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Tag: Immunology

  • UCLA is building a 19-story tower for students near the Westwood campus

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    UCLA, which has been on a campaign to vastly expand student housing around its Westwood campus, is planning a new 19-story tower that 1,150 students can call home.

    Housing has long been a challenge for UCLA students, who have had limited options on campus and faced a pricey housing market in Westwood and nearby neighborhoods.

    In 2022, UCLA announced that it would become the first and only University of California campus to guarantee housing for four years to first-year students and two years for transfer students. The campus now touts housing as a selling point for students it hopes to attract.

    “Residential housing allows us to better ensure that every student gets a good start and is therefore more likely to be successful. So we wanted to give every student an option of having four years,” UCLA’s then-Chancellor Gene Block said in 2022. “That was the dream and it’s finally coming true.”

    The latest new housing complex, recently revealed in a draft environmental study, calls for a 19-story student housing building for UCLA undergraduate students at 901 Levering Ave., adjacent to the school campus.

    The proposed project would provide up to 1,150 beds within a combination of one-, two-, three and primarily four-bedroom units. The cross-shaped tower designed by Seattle architecture firm Mithun would include common courtyard and terrace areas oriented toward Levering Avenue, the study said. On-site parking for residents and guests would not be provided.

    Five existing university-owned apartment buildings with a total of 52 beds would be demolished to make way for the new building. Work could begin as early as next year and be completed by 2030.

    The 901 Levering Terrace tower would be the latest in a string of large student housing projects built by UCLA in recent years, including the 10-story Levering Place apartments next door and a 17-story tower across the street, real estate website Urbanize said. The university is working on another apartment building for 500 students on Gayley Avenue, set to be completed next September for $108 million.

    UCLA’s physical footprint of 419 acres is the smallest among UC’s nine undergraduate campuses and it sits atop some of the state’s priciest real estate, near Brentwood, Bel-Air and Beverly Hills.

    UCLA is also working on converting the former Westside Pavilion shopping center, two miles south of the university at Pico and Westwood boulevards into a research park that will house the California Institute for Immunology and Immunotherapy and the UCLA Center for Quantum Science and Engineering, as well as other science and medicine programs.

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    Roger Vincent

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  • Parenting 101: #MyTealPumpkin : Making Halloween safe for Quebec’s 100,000 children with food allergies

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    Halloween can be difficult for children with allergies, who are often left out due to the distribution of risky treats. Once again this year, for the 9th edition of #MyTealPumpkin, parents, neighbors, friends, and businesses are invited to participate in large numbers so that every child can feel fully included in the celebration. Launched in the United States in 2014, the initiative now shines in about fifteen countries.

    On October 31st, painting a pumpkin turquoise or displaying the visual on your door (available here) signals to families that non-food treats are available for children with allergies, ensuring a safe and inclusive Halloween.

    “Food allergies represent a major and growing health issue in Quebec. When we know that up to 8% of young children in Quebec live with food allergies, and that this segment of the population has increased by 18%, I believe the #MyTealPumpkin initiative takes on its full meaning at Halloween. This activity provides us with a wonderful opportunity to raise awareness among young and old alike,” said Dominique Seigneur, Communications Director at Allergy Quebec, in a press release.

    Anaphylaxis is a severe reaction that can be fatal in just minutes. It is estimated that up to 75% of people allergic to peanuts will be accidentally exposed during their lifetime. In Canada, ten so-called “priority” allergens have been identified (peanuts, wheat, milk, mustard, tree nuts, eggs, fish and shellfish, sesame, soy, and sulfites) as they cause the majority of severe reactions. In total, more than 160 allergenic foods are listed in the country.

    – JC

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  • Major gift accelerates transformation of old mall into UCLA research hub

    Major gift accelerates transformation of old mall into UCLA research hub

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    The reincarnation of a shuttered Los Angeles retail mecca as a sprawling UCLA research center has received a major boost from billionaire philanthropist Dr. Gary Michelson and his wife, Alya, who will give $120 million to ramp up the project.

    Michelson, a spine surgeon and inventor, said the money will help launch the California Institute for Immunology and Immunotherapy, which aims to create breakthrough discoveries that prevent and cure diseases including cancer, heart disease and Alzheimer’s.

    The institute will be a tenant in UCLA Research Park, which is under construction in the former Westside Pavilion. The indoor mall two miles south of the university at Pico and Westwood boulevards was a 1980s icon popular with shoppers and filmmakers before falling out of favor. Most of its stores closed by 2019.

    The shopping center was being converted to offices when the UC Regents bought it for $700 million in January to create the research park. Along with the California Institute for Immunology and Immunotherapy, it will house the UCLA Center for Quantum Science and Engineering, as well as other science and medicine programs.

    By purchasing the former shopping center, UCLA saved years of toil to build such a facility on its campus, which is the smallest of the nine UC undergraduate campuses and has very little room for growth.

    A courtyard view of the UCLA research center now under construction in the former Westside Pavilion shopping center.

    (Brian van der Brug / Los Angeles Times)

    “That building would have gone on the last available piece of property on the UCLA campus,” Michelson said, “and it would have been extraordinarily expensive to build there. As a real estate matter, this was just an extraordinary opportunity.”

    The immunology institute had been planned for years, while a full-scale research park was something “we’ve always dreamed of having … but we always recognized we could never find a piece of property that big close to campus. We had sort of given up on the idea many years ago — and it came alive,” said former UCLA Chancellor Gene Block, who was instrumental in the purchase of the former Westside Pavilion.

    An earlier plan to build the institute on the campus called for tearing down a parking garage, digging a hole deep enough to replace the parking and erecting a new building on top, Block said.

    The gift, through the Michelson Medical Research Foundation, designates $100 million to establish two research entities within the institute, each funded with $50 million; one will focus on rapid vaccine development and the other on harnessing the body’s microbiome to advance human health. The microbiome research will be conducted in collaboration with the new UCLA Goodman-Luskin Microbiome Center, placing it among the largest microbiome research enterprises in the world, the foundation said.

    The foundation is also funding a $20-million endowment to provide research grants to young scientists using novel processes to advance immunotherapy research, human immunology and vaccine discovery.

    The institute will have labs of different sizes meant to serve biotech researchers who can start with small teams that can grow into larger labs if they find success.

    “We’re going to create an entire ecosystem of biotech startups and they’re going to stay right here” and attract other players to the neighborhood, Michelson said. “We’re going to build out an entire ecosystem of biotech all through Westwood.”

    He envisions 5,000 people, including 500 research scientists, working in the institute. Gov. Gavin Newsom estimated in January that it would take more than three years to fully transform the 700,000-square-foot complex, but Michelson hopes to have a large portion of the immunology institute operating in half that time, he said. At 360,000 square feet, the institute will be the research park’s primary tenant.

    The former mall’s 12-screen multiplex movie theater may be converted into lecture halls or performance spaces offering programming across the arts, humanities, sciences and social sciences, the chancellor’s office said.

    Interior view of the new UCLA Research Park.

    An interior view of the UCLA research center now under construction in the former Westside Pavilion shopping center.

    (Brian van der Brug / Los Angeles Times)

    The gift is the Michelsons’ largest single donation in 30 years of philanthropy that includes $50 million to build Michelson Hall at the University of Southern California, which is home to the Michelson Center for Convergent Bioscience. The Michelson name will not be attached to the new UCLA complex, he said, because other philanthropists — perhaps one who donates more than he did — may want the recognition.

    “The gift will change countless lives here and across the globe,” UCLA interim Chancellor Darnell Hunt said.

    The institute will operate as a nonprofit medical research organization funded by a public-private partnership and governed by an independent board that includes UCLA representatives, according to a UC Regents document. The institute will pay UCLA 7.5% of the net revenues generated by the sale of new medicines and other inventions its scientists create, the document said.

    Los Angeles Mayor Karen Bass said the project “has the potential to fundamentally change health outcomes around the world and create good jobs in Los Angeles.”

    The purchase of the former Westside Pavilion marked the third major acquisition for the public university system in Los Angeles in less than two years.

    Seeking to expand its footprint, UCLA announced in June 2023 that it had acquired the Art Deco-style Trust Building in downtown Los Angeles and renamed it UCLA Downtown.

    Nine months prior, the school spent $80 million to buy two other major properties owned by Marymount California University, a small Catholic university that was shuttered last year. The purchase included Marymount’s 24.5-acre campus in Rancho Palos Verdes and an 11-acre residential site in nearby San Pedro.

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    Roger Vincent

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  • West Nile virus detected in Haverhill

    West Nile virus detected in Haverhill

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    HAVERHILL — The state Department of Public Health has confirmed that mosquitoes collected locally tested positive for West Nile virus.

    The mosquitoes were among those captured at a surveillance site in Haverhill, according to Deborah Ketchen, health agent for nearby Merrimac, and that town’s Board of Health.

    The board urged its residents to take proper precautions and offered tips in a news release issued Thursday night, noting that the town’s risk level for the West Nile virus remained the same.

    It was not noted whether these mosquitoes were among those that tested positive for West Nile virus and Eastern equine encephalitis in Haverhill on July 30.

    Haverhill Mayor Melinda Barrett announced on the city’s website Aug. 2 that spraying for mosquitoes would begin three days later in a northeastern section of the community due to the positive findings.

    Trucks from the Northeast Massachusetts Mosquito Control District were to begin spraying the insecticide Zenivex E4 RTU in an area “bounded by Main Street to Kenzoa Avenue to Amesbury Road to Kenzoa Street to Center Street to Millvale Road to East Broadway to Old Ferry Road to Lincoln Avenue to Water Street then back to Main Street,” the city said.

    Public health surveillance is conduced in the state for both mosquito-borne illnesses. The highest risk for contracting WNV or EEE is from late July to the first fall frost, according to Merrimac health officials.

    Mosquitoes receive WNV and EEE by biting infected birds. People and animals contract these diseases by being bitten by an infected mosquito.

    Most people bitten by mosquitoes carrying WNV will either have no symptoms or very mild symptoms and recover on their own. People over age 50 have the highest risk of becoming seriously ill, the Merrimac officials said. Additional monitoring and testing of mosquitoes in Haverhill was expected.

    Merrimac health officials and Barrett encourage the public to take precautions, including using DEET mosquito repellant, wearing long sleeves and pants, and avoiding outdoor activities from dusk to dawn.

    Residents are also asked to check their property for containers of standing water that could attract mosquitoes. Tightly fitted screens are needed for windows and doors, the officials said.

    More information about WNV and EEE is available by calling the state Department of Public Health recorded information line at 1-866-MASS-WNV (1-866-627-7968), or the DPH Epidemiology Program at 617-983-6800.

    A fact sheet is available at mass.gov/doc/wnv-factsheet-english/download.

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  • Merrimac health officials warn about West Nile virus

    Merrimac health officials warn about West Nile virus

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    MERRIMAC — Town health officials ask residents to take precautions after the discovery of mosquitoes infected with West Nile virus in nearby Haverhill.  

    The insects were among those trapped at a specific mosquito surveillance site, Merrimac Health Agent Deborah Ketchen and the town’s Board of Health announced in a news release Thursday night.  

    The state Department of Public Health later confirmed that the mosquitoes tested positive for the potentially deadly virus, the health officials said.

    The Health Board urged local residents to take proper precautions and offered tips, noting that the town’s risk level for West Nile virus remained the same.

    It was not noted whether these mosquitoes were among those that tested positive for West Nile virus and Eastern equine encephalitis in Haverhill on July 30.

    Last week, Newburyport confirmed a case of West Nile virus in the city and urged its residents to take precautions. None of the cases in either community involve infected humans.

    Haverhill Mayor Melinda Barrett announced on the city’s website Aug. 2 that spraying for mosquitoes would begin three days later in a northeastern section of the community due to the positive findings.

    Trucks from the Northeast Massachusetts Mosquito Control District were to begin spraying the insecticide Zenivex E4 RTU in an area “bounded by Main Street to Kenzoa Avenue to Amesbury Road to Kenzoa Street to Center Street to Millvale Road to East Broadway to Old Ferry Road to Lincoln Avenue to Water Street then back to Main Street,” the city said. 

    Public health surveillance is conduced in the state for both mosquito-borne illnesses. The highest risk for contracting WNV or EEE is from late July to the first fall frost, according to Merrimac officials. 

    Mosquitoes receive WNV and EEE by biting infected birds. People and animals contract these diseases by being bitten by an infected mosquito.

    Most people bitten by mosquitoes carrying WNV will either have no symptoms or very mild symptoms and recover on their own. People over age 50 have the highest risk of becoming seriously ill, the Merrimac officials said. Additional monitoring and testing of mosquitoes in Haverhill was expected.

    Merrimac health officials and Barrett encourage the public to take precautions, including using DEET mosquito repellant, wearing long sleeves and pants, and avoiding outdoor activities from dusk to dawn.

    Residents are also asked to check their property for containers of standing water that could attract mosquitoes. Tightly fitted screens are needed for windows and doors, the officials said.   

    More information about WNV and EEE is available by calling the state Department of Public Health recorded information line at 1-866-MASS-WNV (1-866-627-7968), or the DPH Epidemiology Program at 617-983-6800.

    A fact sheet is available at mass.gov/doc/wnv-factsheet-english/download.

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  • Some mosquitoes like it hot

    Some mosquitoes like it hot

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    Newswise — Certain populations of mosquitoes are more heat tolerant and better equipped to survive heat waves than others, according to new research from Washington University in St. Louis.

    This is bad news in a world where vector-borne diseases are an increasingly global health concern. Most models that scientists use to estimate vector-borne disease risk currently assume that mosquito heat tolerances do not vary. As a result, these models may underestimate mosquitoes’ ability to spread diseases in a warming world.

    Researchers led by Katie M. Westby, a senior scientist at Tyson Research Center, Washington University’s environmental field station, conducted a new study that measured the critical thermal maximum (CTmax), an organism’s upper thermal tolerance limit, of eight populations of the globally invasive tiger mosquito, Aedes albopictus. The tiger mosquito is a known vector for many viruses including West Nile, chikungunya and dengue.

    “We found significant differences across populations for both adults and larvae, and these differences were more pronounced for adults,” Westby said. The new study is published Jan. 8 in Frontiers in Ecology and Evolution.

    Westby’s team sampled mosquitoes from eight different populations spanning four climate zones across the eastern United States, including mosquitoes from locations in New Orleans; St. Augustine, Fla.; Huntsville, Ala.; Stillwater, Okla.; St. Louis; Urbana, Ill.; College Park, Md.; and Allegheny County, Pa.

    The scientists collected eggs in the wild and raised larvae from the different geographic locations to adult stages in the lab, tending the mosquito populations separately as they continued to breed and grow. The scientists then used adults and larvae from subsequent generations of these captive-raised mosquitoes in trials to determine CTmax values, ramping up air and water temperatures at a rate of 1 degree Celsius per minute using established research protocols.

    The team then tested the relationship between climatic variables measured near each population source and the CTmax of adults and larvae. The scientists found significant differences among the mosquito populations.

    The differences did not appear to follow a simple latitudinal or temperature-dependent pattern, but there were some important trends. Mosquito populations from locations with higher precipitation had higher CTmax values. Overall, the results reveal that mean and maximum seasonal temperatures, relative humidity and annual precipitation may all be important climatic factors in determining CTmax.

    “Larvae had significantly higher thermal limits than adults, and this likely results from different selection pressures for terrestrial adults and aquatic larvae,” said Benjamin Orlinick, first author of the paper and a former undergraduate research fellow at Tyson Research Center. “It appears that adult Ae. albopictus are experiencing temperatures closer to their CTmax than larvae, possibly explaining why there are more differences among adult populations.”

    “The overall trend is for increased heat tolerance with increasing precipitation,” Westby said. “It could be that wetter climates allow mosquitoes to endure hotter temperatures due to decreases in desiccation, as humidity and temperature are known to interact and influence mosquito survival.”

    Little is known about how different vector populations, like those of this kind of mosquito, are adapted to their local climate, nor the potential for vectors to adapt to a rapidly changing climate. This study is one of the few to consider the upper limits of survivability in high temperatures — akin to heat waves — as opposed to the limits imposed by cold winters.

    “Standing genetic variation in heat tolerance is necessary for organisms to adapt to higher temperatures,” Westby said. “That’s why it was important for us to experimentally determine if this mosquito exhibits variation before we can begin to test how, or if, it will adapt to a warmer world.”

    Future research in the lab aims to determine the upper limits that mosquitoes will seek out hosts for blood meals in the field, where they spend the hottest parts of the day when temperatures get above those thresholds, and if they are already adapting to higher temperatures. “Determining this is key to understanding how climate change will impact disease transmission in the real world,” Westby said. “Mosquitoes in the wild experience fluctuating daily temperatures and humidity that we cannot fully replicate in the lab.”

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    Washington University in St. Louis

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  • Patients Less Likely to Experience Death at Academic and High-Volume Hospitals When Treated with Immunotherapy for Metastatic Cancers

    Patients Less Likely to Experience Death at Academic and High-Volume Hospitals When Treated with Immunotherapy for Metastatic Cancers

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    Newswise — A new study led by Yale Cancer Center researchers at Yale School of Medicine revealed a significant increase in patients starting immunotherapy within one month of death. Using a national clinical database, the researchers focused on patients with metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). They were treated with immune checkpoint inhibitors from the point of FDA approval, through to 2019. The melanoma cohort began treatment in 2012 and the RCC and NSCLC cohorts in 2016.

    The findings were published in JAMA Oncology on January 4.

    “Immunotherapy has revolutionized the field of oncology over the last decade,” said Sajid Khan, MD, senior author of the study and section chief of Hepato-Pancreato-Biliary (HPB) and Mixed Tumors at Yale School of Medicine. “Because survival is substantially improved for many patients treated with these drugs, it’s application has increased across the United States. In our study, we focused on immunotherapy initiation at the end of a patient’s life with cancer metastasis.”

    Because the therapy is relatively new, the study aimed to “offer insights into national prescribing patterns and serve as a harbinger of shifts in the clinical approach to patients with advanced cancer.”

    The study included 20,415 stage IV melanoma patients, 197,331 stage IV NSCLC patients, and 24,625 stage IV RCC patients. Researchers considered each patient’s age, sex, race, and ethnicity as well as the location of metastases and the medical facility where treatment was given.

    “We were interested in gauging how frequently immunotherapy is initiated within the last 30 days of life,” said Khan, a member of Yale Cancer Center and the co-director of Team Science at Yale Center for Clinical Investigation. “Our study found that the initiation of immunotherapy in the last month of a patient’s life has significantly increased in the last 10 years, accounting for one in 14 immunotherapy treatments overall.”

    For patients with metastatic melanoma, the increase was from 0.8% to 4.3%, for NSCLC 0.9% to 3.2%, and for RCC 0.5% to 2.6%. In 2019, these end-of-life-initiated (EOL-I) treatments represented 7.3% of all immunotherapy treatments, indicating a growing application of EOL-I immunotherapy.

    Where patients were treated with immunotherapy mattered. “There were improved survival outcomes when the therapy was administered at academic and high-volume facilities,” said Khan. While patients treated at non-academic or low-volume hospitals had higher odds of receiving EOL-I immunotherapy, patients were less likely to experience death at academic and high-volume hospitals when given immunotherapy for metastatic cancers.

    “Another noteworthy finding was that the outcome for patients receiving immunotherapy towards the end of their life was different depending on the burden of metastasis. Patients with more than three sites of distant metastases are more likely to die within one month of immunotherapy initiation than those with only distant lymph node metastasis.”

    The researchers note that immunotherapy provides a strong overall survival benefit and can salvage patients with metastasis, even those in high-risk sub-groups. The study findings highlight the need for further investigation into the implications of EOL-I immunotherapy with the hope of refining treatment guidelines for the benefit of patients facing metastatic cancer.

    Daniel Kerekes from Yale School of Medicine and Yale Department of Surgery was the study’s first author. Alexander Frey, Elizabeth Prsic, Thuy Tran, James Clune, Mario Sznol, Harriet Kluger, Howard Forman, Robert Becher, and Kelly Olino were Yale co-authors.

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    Yale Cancer Center/Smilow Cancer Hospital

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  • Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

    Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

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    Newswise — Immune cells play an active and intimate role in directing the growth of human lung tissue during development, researchers find, revolutionising our understanding of early lung development and the role of immune cells outside of immunity.

    The research offers new insights for understanding and treating respiratory conditions, such as chronic obstructive pulmonary disease (COPD). Respiratory conditions account for almost 20 per cent of all deaths in children under five years worldwide1.

    The work reveals a surprising coordination between the immune and respiratory systems, much earlier in development than previously thought. This discovery raises questions about the potential role of immune cells in other developing organs across the body.

    Researchers from the Wellcome Sanger Institute, University College London (UCL) and their collaborators at EMBL’s European Bioinformatics Institute used advanced single-cell technologies to map the development of early human lung immune cells over time.

    This study has created a first-of-its-kind immune cell atlas of the developing lung2. It is part of the international Human Cell Atlas3 initiative, which is mapping every cell type in the human body, to transform our understanding of health, infection and disease.

    The findings, published today (15 December) in Science Immunology, will help shed light on the mechanisms behind childhood lung diseases.

    Immune cells make up a substantial portion of the airways and mature lungs, which have critical gas exchange and barrier functions, providing protection against infection of the respiratory tract. However, the roles of immune cells in the developing organ have remained unexplored compared to structural or lining cell types. Recent discoveries confirm the presence of immune cells in human lungs as early as five weeks into development4.

    To explore whether the immune system might influence how lungs grow, the team studied immune cells in early human lungs from 5 to 22 weeks of development. They used various techniques, including single-cell sequencing and experiments with lung cell cultures, to see if immune cells could affect lung cell development.

    They identified key regulators of lung development, including signalling molecule IL-1β and IL-13 that facilitate the coordination of lung stem cells differentiating into specialised mature cell types5.

    The researchers detected an infiltration of innate, followed by adaptive immune cells. Innate cells included innate lymphoid cells (ILCs), natural killer (NK) cells, myeloid cells and progenitor cells. With respect to adaptive immune cells, as well as T cells, both developing and mature B lineage cells were detected, indicating that the lung environment supports B cell development.

    The findings fundamentally change the understanding of the immune and epithelial interactions that are crucial for foetal lung maturation. They also suggest that early immune disturbances could manifest as paediatric lung disease.

    These new insights into mechanisms in early lung formation will also contribute to the development of new therapeutic approaches for regenerating damaged lung tissue and restoring lung function.

    Dr Peng He and Dr Jo Barnes, co-first authors of the study at the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute, and UCL Division of Medicine respectively, said: “By adopting a focused strategy in mapping the immune system, we reveal a symbiotic relationship between immune cells and developing lungs. These detailed insights open the door to potential regenerative therapies in not only the lung, but in other vital human organs.”

    Dr Marko Nikolić, senior author of the study at UCL Division of Medicine and honorary consultant in respiratory medicine, said: “We now know immune-epithelial crosstalk is a feature of early lung development. This vital baseline of healthy lung development will help us understand what happens when lung developmental processes get disrupted, for example in preterm births, which can lead to respiratory deficiencies.”

    Dr Kerstin Meyer, senior author of the study at the Wellcome Sanger Institute, said: “The active participation of immune cells expands the possibilities for understanding and addressing impaired lung formation. What is super exciting about this mechanism is that it may well apply in other organ systems too.”

    Dr Sarah Teichmann, senior author of the study at the Wellcome Sanger Institute and Co-founder of the Human Cell Atlas, said: “If we are to fully understand the root causes of disease, we require a complete view of cells at all stages in the human body. This important contribution towards a comprehensive Human Cell Atlas will be a valuable reference for studying lung diseases.”

    ENDS

    Notes to Editors:

    1. https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3147
    2. The researchers analysed human embryonic and foetal lung tissue between 5 and 22 weeks post-conception. Human embryonic tissue was provided by the Joint MRC/Wellcome Trust Human Developmental Biology Resource (www.hdbr.org)
    3. The Human Cell Atlas (HCA) is an international collaborative consortium which is creating comprehensive reference maps of all human cells—the fundamental units of life—as a basis for understanding human health and for diagnosing, monitoring, and treating disease. The HCA is likely to impact every aspect of biology and medicine, propelling translational discoveries and applications and ultimately leading to a new era of precision medicine.
      The HCA was co-founded in 2016 by Dr Sarah Teichmann at the Wellcome Sanger Institute (UK) and Dr Aviv Regev, then at the Broad Institute of MIT and Harvard (USA). A truly global initiative, there are now more than 3,100 HCA members, from 98 countries around the world. https://www.humancellatlas.org
    4. https://www.cell.com/cell/fulltext/S0092-8674(22)01415-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867422014155%3Fshowall%3Dtrue
    5. Experimentation showed that IL-1β, a cytokine produced by immune cells, directly induced airway epithelial progenitor cells to differentiate into mature lung lining cells. They do this by decreasing SOX9 expression and proliferation, driving lung epithelial progenitor cells to stop self-renewal.

    Publication:
    J.L. Barnes et al. (2023) ‘Early human lung immune cell development and its role in epithelial cell fate.’ Science Immunology. DOI: 10.1126/sciimmunol.adf9988

    Funding:
    This research was supported by Wellcome. For full funding acknowledgements, please refer to the publication.

    Selected websites:

    About UCL (University College London)
    UCL was founded in 1826. We were the first English university established after Oxford and Cambridge, the first to open up university education to those previously excluded from it, and the first to provide systematic teaching of law, architecture and medicine. We are among the world’s top universities, as reflected by performance in a range of international rankings and tables. UCL currently has over 39,000 students from 150 countries and over 12,500 staff. Our annual income is more than £1 billion. www.ucl.ac.uk | Follow us on Twitter @uclnews | Watch our YouTube channel YouTube.com/UCLTV

    The Wellcome Sanger Institute
    The Wellcome Sanger Institute is a world leader in genomics research. We apply and explore genomic technologies at scale to advance understanding of biology and improve health. Making discoveries not easily made elsewhere, our research delivers insights across health, disease, evolution and pathogen biology. We are open and collaborative; our data, results, tools, technologies and training are freely shared across the globe to advance science.

    Funded by Wellcome, we have the freedom to think long-term and push the boundaries of genomics. We take on the challenges of applying our research to the real world, where we aim to bring benefit to people and society.

    Find out more at www.sanger.ac.uk or follow us on Twitter, Instagram, Facebook, LinkedIn and on our Blog.

    About Wellcome
    Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health. https://wellcome.org/

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    Wellcome Trust Sanger Institute

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  • Cell Therapy Appears Safe and Effective for Lymphoma in Remission

    Cell Therapy Appears Safe and Effective for Lymphoma in Remission

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    DOWNLOADABLE VIDEO HERE

    Newswise — MIAMI, FLORIDA (EMBARGOED UNTIL SUNDAY, DEC. 10, 2023 AT 8:00 P.M. ET) – A study led by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine suggests that CAR-T immunotherapy remains a viable option for patients who have lymphoma that goes into remission before the cell therapy begins.

    While the study doesn’t answer the question of whether cell therapy in remission is the right choice, it does say that it’s not the wrong choice.

    “I don’t think it answers the question of: Should we give these patients cell therapy? But I think it answers the question that we can – that it’s safe and that it’s a reasonable strategy when you’re in that spot,” said Trent Wang, D.O., a Sylvester hematologist and cellular therapy specialist who will present study findings in an oral presentation at the 65th ASH Annual Meeting and Exposition, the American Society of Hematology’s conference taking place in San Diego, California, Dec. 9-12.

    Most patients receiving cell therapy, a form of immunotherapy that uses immune cells engineered to recognize and attack the patient’s cancer, desperately need it. For some, it comes after many other treatments have failed. But Wang noticed an odd phenomenon in the past few years when treating lymphoma patients with this form of therapy: Some of his patients went into complete remission before the cells ever touched their bodies.

    This uncommon scenario occurs during the process of getting to cell therapy, which in the case of Wang’s study uses a kind of engineered immune cell known as CAR-T cells. When a patient starts the process, there’s a waiting period of three to five weeks before they get the treatment. Insurance approval is needed, and the cells themselves need to be manufactured from the patient’s own cells. But many of these patients are very sick with their cancer, so physicians will often treat them with a short course of chemotherapy or other drugs to tamp down the symptoms.

    A small handful of these patients end up in remission during this waiting period treatment, the clinicians have found.

    “That prompted this dilemma: Now what are we supposed to do?” Wang said. “Should we change the plan or give the therapy anyway? We just didn’t have a lot of information on this scenario.”

    Wang said more often than not his team would proceed with the cell therapy in these cases, mainly to prevent yet another stretch of time where the patients’ cancer might come back again. But it didn’t feel like a very informed decision.

    Wang and his colleagues noticed that their patients who received the cells while in remission tended to fare well after their infusion. But they didn’t know if those results would hold up in an analysis of a larger group. They proposed a research study to the Center for International Blood & Marrow Transplant Research, a nationwide registry that tracks patients who have received transplants and/or cell therapies.

    The study included data from 134 patients in the registry who had gone into complete remission in the waiting period before receiving their cell therapy. To find that group, the scientists screened the records for more than 5,000 cell therapy patients.

    They found that this group of patients had a 43% probability of progression-free survival over the two years following their treatment, about the same percentage as patients in the registry who were not in remission when they received CAR-T. However, the patients in remission had very low levels of toxicities related to their cell therapies, namely an immune overreaction known as cytokine release syndrome and neurotoxicity, two side effects that can sometimes accompany CAR-T cell therapy.

    The study used data from patients treated with CAR-T cell therapy between 2015 to 2021, and current frequencies of specific cell therapy use are slightly different from those that were used in practice just a few years ago, Wang said. Next, the researchers want to explore the data paralleling more recent treatment trends.

    Authors: Wang, first author, and Antonio M. Jimenez Jimenez, M.D., last author, are Sylvester researchers. Co-authors include Kwang Wooahn, Ph.D., Manmeet Kaur, and Mehdi Hamadani, M.D., Medical College of Wisconsin; Mazyar Shadman, M.D., Fred Hutchinson Cancer Center, Seattle; Alex F. Herrera, M.D., City of Hope, Duarte, California; and Craig S. Sauter, M.D., Taussig Cancer Institute, Cleveland.

    Conflicts and disclosures: A full list of disclosures is included with the abstract.

    # # #

    Presentation Title: 615 Chimeric Antigen Receptor (CAR) T Cell Infusion for Large B Cell Lymphoma in Complete Remission: A Center for International Blood & Marrow Transplant Research (CIBMTR) Analysis 

    DOWNLOADABLE VIDEO HERE 

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    Sylvester Comprehensive Cancer Center

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  • Lessons Learned From ADLM’s COVID Immunity Study Could Improve Research on Future Pandemics

    Lessons Learned From ADLM’s COVID Immunity Study Could Improve Research on Future Pandemics

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    Newswise — WASHINGTON – A special report published today in the Association for Diagnostics & Laboratory Medicine’s (ADLM’s, formerly AACC’s) The Journal of Applied Laboratory Medicine describes the design, operations, and methodology of the COVID Immunity Study, a large-scale scientific study by ADLM that took place in September 2021. By detailing the design of this novel study, the special report aims to facilitate similar studies by other scientific societies. These could fill in gaps in infectious disease research and potentially improve the global response to future pandemics.   

    View the full report here: https://academic.oup.com/jalm/advance-article/doi/10.1093/jalm/jfad089/7416439

    The COVID Immunity Study is the first scientific study performed by a professional association that combines an online health survey, on-site blood collection, off-site testing and analysis, provision of SARS-CoV-2 testing results to participants, and sample banking to address questions of SARS-CoV-2 immunity. Large-scale epidemiological studies such as this are crucial for understanding how viruses evolve and for making informed public health decisions. Because these types of studies demand tremendous resources, they are typically conducted by government agencies or as collaborative efforts by academic research groups. As the COVID Immunity Study shows, though, scientific societies also have the resources and expertise to perform large-scale epidemiological studies. These organizations are also in a position to investigate potentially important lines of inquiry that traditionally funded research can’t look into. While several papers that were either recently published or in preparation focus on the results of the COVID Immunity Study, this special report discusses the methodology of the study and unique challenges it encountered with the goal of providing a model for other scientific societies to follow.

    The COVID Immunity Study was mainly conducted at the 2021 AACC Annual Scientific Meeting in Atlanta. Blood was drawn on-site from 698 participants, who provided consent and completed general health and COVID-19 questionnaires beforehand. A portion of each sample was sent to Quest Diagnostics for T-cell function analysis, while serum and plasma were obtained from the remaining samples, which were stored at Centers for Disease Control and Prevention (CDC) facilities in Atlanta and made available to medical and research communities. Partnerships between ADLM staff and subject-matter experts such as clinical laboratory scientists and immunologists, as well as state and local health departments, were crucial to the success of the study.

    The study group encountered several logistical and practical challenges during the execution of the COVID Immunity Study, including staffing shortages due to the pandemic, the lack of prior on-site facilities for a scientific study, unavailable and back-ordered supplies, and the large number of participants required to donate blood. Though the COVID Immunity Study was successfully planned and executed in 6 months, the paper’s authors recommend a 12-month or longer period for such a study, especially if conducted in pandemic conditions.

    “ADLM believes that the unique makeup of scientific societies positions them well to ask and answer pressing questions in their fields that might otherwise not fall into a clear area of interest by traditional research funding sources,” the report authors said. “We hope that this paper will serve as a reference — and set a precedent — for member-based organizations to contribute to future such scientific studies.”

    About the Association for Diagnostics & Laboratory Medicine (ADLM)

    Dedicated to achieving better health through laboratory medicine, ADLM (formerly AACC) brings together more than 70,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, ADLM has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.myadlm.org.

    The Journal of Applied Laboratory Medicine (academic.oup.com/jalm) is published online by ADLM. This international, peer-reviewed publication showcases applied research on clinically relevant laboratory topics as well as commentary on the practice of clinical chemistry and laboratory medicine.

     

     

     

     

     

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  • فهم العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) وآثارها الجانبية المحتملة

    فهم العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) وآثارها الجانبية المحتملة

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    جاكسونفيل، فلوريدا — العلاج المناعي يسخر جهاز المناعة في الجسم لمحاربة السرطان. العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (العلاج بخلايا CAR-T) هو شكل من أشكال العلاج المناعي الذي يقوم فيه أخصائيو الرعاية الصحية بإزالة الخلايا التائية للشخص — خلايا الدم البيضاء المعروفة باسم الخلايا اللمفية التي تشارك في استجابة الجهاز المناعي — وتعديلها وراثيًا لإنتاج مستقبلات المستضد الخيمرية (CARs). يتم بعد ذلك حقن الخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) مرة أخرى في مجرى دم المريض، حيث تستهدف الخلايا السرطانية وتقتلها.

    يقول دكتور محمد خرفان دباجة، دكتور في الطب اختصاصي الدَّمَويات والأورام في مايو كلينك: “يعد العلاج بخلايا CAR-T من بين أكثر المجالات الواعدة لعلاج السرطان، مع العديد من قصص النجاح في جميع أنحاء العالم. لقد أعطى أملًا جديدًا للمرضى الذين كانت لديهم في السابق خيارات محدودة.”

    من مؤهل للعلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T)؟

    وافقت إدارة الأدوية الفيدرالية على العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) لعلاج سرطانات الدم التالية:

    الأشخاص الذين يعانون من هذه التشخيصات والذين لم يستجب مرضهم للعلاج (المقاومة) أو الذين انتكس مرضهم قد يكونون مؤهلين للعلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T). يجب أن يخضع المرضى لتقييم شامل لتحديد ما إذا كان العلاج بخلايا CAR-T هو الخيار الأفضل للعلاج.

    كم يستغرق الأمر من الوقت لإتمام العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T)؟

    تعتبر عملية العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) معقدة ويمكن أن تستغرق عدة أسابيع. يعاني معظم الأشخاص من رد فعل تجاه الخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) مما قد يتطلب منهم البقاء في المستشفى للمراقبة والإدارة.

    يقول الدكتور خرفان دباجة: “يجب على الأشخاص الذين يخططون لتلقي العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) أن يتوقعوا البقاء في المستشفى بعد حقن الخلايا لعدة أيام حتى يتمكن فريق الرعاية الخاص بهم من مراقبة استجابتهم للعلاج”.

    ما الآثار الجانبية المحتملة للعلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T)؟

    في حين أن الآثار الجانبية لعلاج الخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) قابلة للعكس بشكل عام، إلا أن الدكتور خرفان دباجة يقول إنها قد تشمل:

    • متلازمة إطلاق السيتوكين (CRS): تعد متلازمة إطلاق السيتوكين (CRS) أحد الآثار الجانبية الأكثر شيوعًا للعلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T)، وتنجم عن الاستجابة المناعية التي تحدث عند إدخال الخلايا التائية المعدلة إلى مجرى دم المريض. عندما تبدأ الخلايا التائية في استهداف الخلايا السرطانية، فإنها تطلق عددًا كبيرًا من السيتوكينات – وهي بروتينات يمكن أن تتسبب في المبالغة في رد فعل الجهاز المناعي. وقد يؤدي هذا إلى الحُمّى، وانخفاض ضغط الدم، وآلام في العضلات وأعراض أخرى تشبه أعراض الإنفلونزا. في الحالات الشديدة، يمكن أن نسبب متلازمة إطلاق السيتوكين (CRS) فشل الأعضاء وحتى أن تكون مميتة. يمكن التحكم في معظم الأعراض المرتبطة بمتلازمة إطلاق السيتوكين (CRS) باستخدام الأدوية والمراقبة الحثيثة.
    • السمية العصبية: قد يعاني بعض المرضى من تأثير عصبي يعرف باسم السمية العصبية بعد تلقي العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T). هذه حالة خطيرة محتملة تؤثر فيها الاستجابة المناعية للعلاج على الجهاز العصبي المركزي. في حين أن السبب الدقيق للتسمم العصبي غير مفهومًا جيدًا، تشير بعض الدراسات إلى أنه يرتبط جزئيًا بخطورة متلازمة إطلاق السيتوكين (CRS). يمكن أن تشمل الأعراض الارتباك والنوبات المَرَضية وصعوبة التحدث أو المشي. يتم حل معظم حالات السمية العصبية من خلال المراقبة الحثيثة دون آثار جانبية طويلة المدى.
    • اضطرابات الدم: يمكن أن يؤدي العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) إلى تغيرات في الدم يمكن أن تؤدي إلى فقر الدم ، ونقص الصفيحات (انخفاض عدد الصفائح الدموية) واضطرابات الدم الأخرى. عادةً ما تكون هذه التأثيرات قصيرة الأمد وتختفي من تلقاء نفسها بمرور الوقت، ولكنها قد تكون أكثر خطورة لدى بعض المرضى.
    • العَدوى: قد يكون الأشخاص الذين يتلقون العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) أكثر عرضة للإصابة بالعدوى، خاصة خلال الأسابيع القليلة الأولى بعد العلاج عندما يعمل الجهاز المناعي وقتًا إضافيًا لمحاربة السرطان. يمكن أن يبقى الأشخاص الذين يعانون من انخفاض عدد خلايا الدم البيضاء أكثر عرضة لخطر الإصابة بالعَدوى لبعض الوقت. ويجب مراقبتهم عن قرب بحثًا عن مؤشرات العَدوى، بما في ذلك الحُمّى والقشعريرة والشعور العام بالتوعك.
    • الآثار الجانبية طويلة المدى: نظرًا لأن العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) لا يزال جديدًا نسبيًا، فإن المتخصصين في الرعاية الصحية لا يعلمون بعد النطاق الكامل لآثاره الجانبية طويلة المدى.

    يشجع الدكتور خرفان دباجة الأشخاص الذين يفكرون في العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) على التحدث مع فرق الرعاية الخاصة بهم حول المخاطر والفوائد المحتملة وأي مخاوف بشأن صحتهم على المدى الطويل. ويوصي أيضًا بالسعي للحصول على تقييم للعلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T) في مركز علاج السرطان الشامل.

    يقول الدكتور: “إذا كنت تعتقد أنك أو شخص عزيز لديك قد تكون مرشحًا لهذا العلاج، فمن الأفضل التواصل مع فريق رعاية لديه خبرة في علاج العديد من مرضى السرطان الذين يتلقون العلاج بالخلايا التائية المستقبلة للمستضدات الخيمرية (CAR-T)”.

    تم نشر هذه المقالة في الأصل على مدونة مركز مايو كلينك الشامل للسرطان.

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    نبذة عن مايو كلينك
    مايو كلينك هي مؤسسة غير ربحية تلتزم بالابتكار في الممارسات السريرية والتعليم والبحث وتوفير التعاطف والخبرة لكل مَن يحتاج إلى الاستشفاء والرد على استفساراته. لمعرفة المزيد من أخبار مايو كلينك، تفضَّل بزيارة شبكة مايو كلينك الإخبارية.

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    Mayo Clinic

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  • Bacteria, stay out!

    Bacteria, stay out!

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    Hospital germs and pathogens are not always transmitted directly from person to person. They can also spread via germ-contaminated surfaces and objects.

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    Empa, Swiss Federal Laboratories for Materials Science and Technology

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  • Nutrient found in beef and dairy improves immune response to cancer

    Nutrient found in beef and dairy improves immune response to cancer

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    Newswise — Trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep, improves the ability of CD8+ T cells to infiltrate tumors and kill cancer cells, according to a new study by researchers from the University of Chicago.

    The research, published this week in Nature, also shows that patients with higher levels of TVA circulating in the blood responded better to immunotherapy, suggesting that it could have potential as a nutritional supplement to complement clinical treatments for cancer.

    “There are many studies trying to decipher the link between diet and human health, and it’s very difficult to understand the underlying mechanisms because of the wide variety of foods people eat. But if we focus on just the nutrients and metabolites derived from food, we begin to see how they influence physiology and pathology,” said Jing Chen, PhD, the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the new study. “By focusing on nutrients that can activate T cell responses, we found one that actually enhances anti-tumor immunity by activating an important immune pathway.”

    Finding nutrients that activate immune cells

    Chen’s lab focuses on understanding how metabolites, nutrients and other molecules circulating in the blood influence the development of cancer and response to cancer treatments. For the new study, two postdoctoral fellows, Hao Fan, PhD and Siyuan Xia, PhD, both co-first authors, started with a database of around 700 known metabolites that come from food and assembled a “blood nutrient” compound library consisting of 235 bioactive molecules derived from nutrients. They screened the compounds in this new library for their ability to influence anti-tumor immunity by activating CD8+ T cells, a group of immune cells critical for killing cancerous or virally infected cells.

    After the scientists evaluated the top six candidates in both human and mouse cells, they saw that TVA performed the best. TVA is the most abundant trans fatty acid present in human milk, but the body cannot produce it on its own. Only about 20% of TVA is broken down into other byproducts, leaving 80% circulating in the blood. “That means there must be something else it does, so we started working on it more,” Chen said.

    The researchers then conducted a series of experiments with cells and mouse models of diverse tumor types. Feeding mice a diet enriched with TVA significantly reduced the tumor growth potential of melanoma and colon cancer cells compared to mice fed a control diet. The TVA diet also enhanced the ability of CD8+ T cells to infiltrate tumors.

    The team also performed a series of molecular and genetic analyses to understand how TVA was affecting the T cells. These included a new technique for monitoring transcription of single-stranded DNA called kethoxal-assisted single-stranded DNA sequencing, or KAS-seq, developed by Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry at UChicago and another senior author of the study. These additional assays, done by both the Chen and He labs, showed that TVA inactivates a receptor on the cell surface called GPR43 which is usually activated by short-chain fatty acids often produced by gut microbiota. TVA overpowers these short-chain fatty acids and activates a cellular signaling process known as the CREB pathway, which is involved in a variety of functions including cellular growth, survival, and differentiation. The team also showed that mouse models where the GPR43 receptor was exclusively removed from CD8+ T cells also lacked their improved tumor fighting ability.

    Finally, the team also worked with Justin Kline, MD, Professor of Medicine at UChicago, to analyze blood samples taken from patients undergoing CAR-T cell immunotherapy treatment for lymphoma. They saw that patients with higher levels of TVA tended to respond to treatment better than those with lower levels. They also tested cell lines from leukemia by working with Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine, and saw that TVA enhanced the ability of an immunotherapy drug to kill leukemia cells.

    Focus on the nutrients, not the food

    The study suggests that TVA could be used as a dietary supplement to help various T cell-based cancer treatments, although Chen points out that it is important to determine the optimized amount of the nutrient itself, not the food source. There is a growing body of evidence about the detrimental health effects of consuming too much red meat and dairy, so this study shouldn’t be taken as an excuse to eat more cheeseburgers and pizza; rather, it indicates that nutrient supplements such as TVA could be used to promote T cell activity. Chen thinks there may be other nutrients that can do the same.

    “There is early data showing that other fatty acids from plants signal through a similar receptor, so we believe there is a high possibility that nutrients from plants can do the same thing by activating the CREB pathway as well,” he said.

    The new research also highlights the promise of this “metabolomic” approach to understanding how the building blocks of diet affect our health. Chen said his team hopes to build a comprehensive library of nutrients circulating in the blood to understand their impact on immunity and other biological processes like aging.

    “After millions of years of evolution, there are only a couple hundred metabolites derived from food that end up circulating in the blood, so that means they could have some importance in our biology,” Chen said. “To see that a single nutrient like TVA has a very targeted mechanism on a targeted immune cell type, with a very profound physiological response at the whole organism level—I find that really amazing and intriguing.”

    The study, “Trans-vaccenic acid reprograms CD8+ T cells and anti-tumor immunity,” was supported by the National Institutes of Health (grants CA140515, CA174786, CA276568, 1375 HG006827, K99ES034084), a UChicago Biological Sciences Division Pilot Project Award, the Ludwig Center at UChicago, the Sigal Fellowship in Immuno-oncology, the Margaret E. Early Medical Research Trust, the AASLD Foundation a Harborview Foundation Gift Fund, and the Howard Hughes Medical Institute.

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    University of Chicago Medical Center

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  • Antibodies to Cow’s Milk Linked to Increased Risk of Cardiovascular Death

    Antibodies to Cow’s Milk Linked to Increased Risk of Cardiovascular Death

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    BYLINE: Analyses led by Corinne Keet, MD, PhD, at the University of North Carolina School of Medicine, of two longitudinal studies reveal how an increased level of an antibody called immunoglobin (IgE) to cow’s milk is associated to cardiovascular-related death.

    Newswise — CHAPEL HILL, NC – Sensitivity to common food allergens such as cow’s milk and peanuts could be an important and previously unappreciated cause of heart disease, new research suggests – and the increased risk for cardiovascular death includes people without obvious food allergies.

    In a paper published in The Journal of Allergy and Clinical Immunology that describes analyses led by Corinne Keet, MD, PhD, pediatric allergy and immunology professor in the UNC Department of Pediatrics of two longitudinal studies, the authors show that the people who produced IgE antibodies to cow’s milk and other foods were at significantly increased risk of cardiovascular mortality. This was true even when traditional risk factors for heart disease, such as smoking, high blood pressure, and diabetes were accounted for. The strongest link was for cow’s milk, but IgE to other allergens such as peanut and shrimp were also significant among those who eat the foods.

    This troubling finding represents the first time that IgE antibodies to common foods have been linked to increased risk of cardiovascular mortality, the researchers report. The findings do not conclusively prove that food antibodies are causing the increased risk, but the work builds on previous studies connecting allergic inflammation and heart disease.

    “People who had an antibody called IgE to foods that they regularly eat seemed to be at increased risk for dying from heart disease,” said Keet, who is the corresponding author of the paper. “We were surprised by these findings because it is very common to have IgE to foods (about 15% of American adults have IgE to common food allergens), and most people don’t have any symptoms when they eat the food. As allergists, our thinking has been that it is not important if people have IgE to foods, as long as they don’t have symptoms when they eat the food,” she said.

    Funded by the National Institute of Allergy and Infectious Disease and an AAAAI Faculty Development Award to her collaborator Jeff Wilson at the University of Virginia, this research used two methods to examine the association between IgE sensitization to foods and cardiovascular mortality. Data from 4,414 adults who participated in The National Health and Examination Survey (NHANES) and 960 participants in the Wake Forest site of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort were used. Participants were enrolled in MESA from 2000-2002 and followed for up to 19 years. Participants were enrolled in NHANES from 2005 to 2006 and data on mortality up to 14 years were tracked. Total and specific IgE was measured to cow’s milk, egg, peanut, shrimp, and a panel of aeroallergens for the NHANES group. IgE to cow’s milk, alpha-gal, peanut, dust mite and timothy grass were measured in the MESA group. In NHANES, 229 cardiovascular deaths were recorded and 960 deaths from MESA were also reported. Milk sensitization was particularly associated in both NHANES & MESA. Researchers also discovered that food sensitization to shrimp and peanut were both additional risk factors for heart disease.

    It is also important to note that associations in the findings related to food sensitization rather than clinical allergy. Although researchers did not have access to information about clinical food allergy in either cohort, they expect that individuals who report regularly eating a food allergen on food frequency questionnaires were not showing symptoms of a food allergy. Thus, the findings that showed how associations were strengthened when researchers excluded those who avoided the food suggest that these findings were most relevant to those who have not been diagnosed with food allergy. Keet says the results raise questions about whether these apparently non-allergic individuals may have long-term consequences from consuming foods to which they are sensitized.

    The study states that aside from two recent reports linking IgE to the unusual carbohydrate allergen alpha-gal to coronary artery disease, cardiovascular disease had not previously been identified as a long-term complication of food sensitization. However, there is now substantial evidence for the importance of allergic-type immune pathways in normal cardiac physiology and heart disease. Because discovering the link between milk sensitization with cardiovascular mortality is new, Keet says there’s more to explore as far as the relevance of food sensitization and diet in cardiovascular disease development.

    “More research needs to be done about how sensitization to common food allergens is related to cardiovascular disease,” she said. “While this study provides good evidence of an association between sensitization to these allergens and death from cardiovascular disease, there is much work to be done to understand if this is a causal relationship.”

    Media contact: Brittany T. Phillips, Communications Specialist, UNC Health | UNC School of Medicine

     

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    University of North Carolina Health Care System

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  • Enhancing cancer immunotherapy using modified CAR-T cells.

    Enhancing cancer immunotherapy using modified CAR-T cells.

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    Newswise — CAR-T cell therapy is a last hope for many patients with blood, bone marrow or lymph gland cancer when other treatments such as chemotherapy are unsuccessful. A limiting factor of this otherwise very effective and safe therapy is that the cells used in the process quickly reach a state of exhaustion. Researchers at the University of Freiburg have now been able to prevent this exhaustion and thus significantly improve the effect of the therapy in a preclinical animal model. The new results have been published in the journal Nature Immunology.

    Using the body’s own defences against cancer
    CAR-T cells are one of the personalised cancer therapies and have been used in specialised centres in Europe since 2018. In this complex treatment, immune cells, or more precisely T cells, are taken from the blood of cancer patients, genetically engineered in the laboratory with a chimeric antigen receptor (CAR) and then re-administered. The receptor helps the T cells to identify and kill cancer cells. As a result, the therapy utilises the body’s own cells to permanently eradicate the cancer.

    A simplified T-cell receptor
    The CAR functions like a sensor with which the T cell recognises characteristic surface features of cancer cells. The synthetic CAR consists in part of elements of the natural T cell receptor, but its structure is greatly simplified in comparison. The CAR has only one of the four different subunits that transmit the signals that trigger the activation of the immune response in unmodified T cells.

    “The CARs authorised by the drug authorities all use the so-called zeta chain, which triggers a particularly strong activation of the T cell as soon as the CAR binds to the surface of a cancer cell. Whether the other three signalling chains of the T-cell receptor – gamma, delta and epsilon – can also be used for CARs has not yet been investigated,” explains Prof. Dr Susana Minguet, who led the current study together with Prof. Dr Wolfgang Schamel. Both are members of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies at the University of Freiburg and are researching how the various subunits of the T cell receptor transmit signals in order to trigger an immune response.

    For their current study, the researchers produced four types of CAR-T cells, each expressing a CAR with each of the four signalling subunits, and tested them in a mouse model of leukaemia. “Surprisingly, the zeta chain, the domain used in clinically applied CAR-T cells, showed a lower anti-tumour effect than the other three domains. These eliminated the cancer cells in the leukaemia model significantly better,” explains Schamel.

    Strong activation is a downside
    The researchers explain the result by the fact that although the zeta chain transmits a strong activating signal to the cell, this also quickly exhausts the cell. “It’s as if we were making the cells run an ultramarathon at maximum speed,” explains Minguet. In contrast, the delta chain, which showed the best efficacy in the current study, triggers an inhibitory signal parallel to the activation of the T cell. “This allows the immune cell to run at its optimum speed,” says Minguet.

    Results relevant to clinical research
    “Our results show that CARs that use one of the other signalling domains instead of the zeta chain could mitigate or prevent the disadvantages of existing therapies with CAR-T cells,” summarises Schamel. The researchers conclude that the development of new CAR therapies should therefore consider strategies that can achieve a more balanced immune response.

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  • Pathologic Scoring Shows Promise for Assessing Lung Tumor Therapy Response

    Pathologic Scoring Shows Promise for Assessing Lung Tumor Therapy Response

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    **EMBARGOED UNTIL 8 P.M. ET SATURDAY, NOV. 4**

    Newswise — A new pathologic scoring system that accurately assesses how much lung tumor is left after a patient receives presurgical cancer treatments can be used to predict survival, according to new research led by investigators at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center and the Mark Foundation Center for Advanced Genomics and Imaging at the Johns Hopkins University.

    The study shows that pathologic assessment of residual viable tumor (RVT) in patients treated with immunotherapy and chemotherapy before lung cancer surgery provides a robust and efficient evaluation of patient treatment response that may be useful to guide patient therapy and predict survival. This latter finding supports pathologic evaluation of tumors as an early clinical trial endpoint and a surrogate of survival for potential accelerated regulatory approvals.

    The results were published on Nov. 4 in the journal Nature Medicine and simultaneously presented by senior study author Janis Taube, M.D., M.Sc., director of the Division of Dermatopathology at the Johns Hopkins University School of Medicine and a member of the Kimmel Cancer Center, at the Society for Immunotherapy of Cancer annual meeting in San Diego.

    Immunotherapies harness a patient’s immune system to target their tumors. These powerful drugs are often paired with conventional chemotherapies to help shrink a patient’s tumors before surgery, increasing the likelihood of successfully eliminating the cancer. To gauge treatment success, oncologists typically rely on radiologic imaging of the remaining tumor, but the results aren’t always as accurate in early-stage tumors as they are for more advanced cancers. More recently, circulating tumor DNA (ctDNA) clearance, which uses genetic sequencing to detect lung cancer-associated mutations in patient blood samples, has also shown promise, but is not yet widely available.

    For the new study, investigators performed a new analysis on data from the randomized, phase 3 CheckMate 816 study. That study found that treating presurgical non-small cell lung cancer patients with immunotherapy (nivolumab) plus chemotherapy improved event-free survival. This important surrogate endpoint can help predict long-term survival and pathologic complete response, which measures whether any tumor is left.

    “Most studies have focused on whether you have no tumor left or less than or equal to 10% of the tumor left, which is called a major pathologic response,” says lead study author Julie Stein Deutsch, M.D., an assistant professor of dermatology at Johns Hopkins.

    During the study, the investigators used a new approach, which measures residual tumor in patients who received neoadjuvant therapy, to predict outcomes in patients with a greater range of treatment responses. They used immune-related pathologic response criteria (irPRC) to look for pathologic changes that indicated the tumor had been present in the tissue before immunotherapy but was destroyed by the treatment, allowing them to measure what percentage of the tumor was left, or the RVT, ranging from 0% to 100%.

    As a result, they were able to separate patients into three groups based on how much tumor was left. In the future, data such as these may help guide the next round of clinical trials and ultimately help oncologists decide how to treat individuals in these subgroups, Deutsch says. For example, patients with no tumor left may be able to skip postsurgical immunotherapy or have a relatively limited amount, while individuals in the intermediate group may need to continue immunotherapy for longer. Those who showed a very limited response may need to switch to a new therapy or add a new therapy to their regimen. The team’s next steps will include identifying the most clinically meaningful cutoffs for RVT.

    They also looked beyond the primary tumor and used RVT to assess the immunotherapy effect on tumor in the lymph nodes, which showed additive value with the primary tumor for predicting survival. Long term, it may also be possible to strategically combine pathology, radiology and ctDNA results for the longitudinal monitoring of treatment efficacy.

    Already, the investigators demonstrated the pathologic scoring system can assess 10 types of tumors, including lung, skin and colorectal cancers, which could be another advantage over other tumor scoring systems.

    “The common features seen across these multiple tumor types means that pathologists don’t have to switch to different scoring systems for assessing pathologic response. This is similar to what already exists in radiology, where the RECIST system is used across all tumor types for determining objective response to therapy,” Taube says, noting that pathologists already are completing the necessary workflows as part of standard procedures when assessing surgically removed tumors. Assessing RVT is inexpensive and uses tools and supplies commonly used by pathologists, Deutsch says, which may also make it accessible for those working in low-resource settings.

    “It is important that as these immunotherapies move into clinical trials and become standard of care, pathologists worldwide have a standard scoring system for the assessment of treatment response,” Taube says. 

    Study co-authors were Ashley Cimino-Mathews, Elizabeth Thompson, Patrick M. Forde, Daphne Wang, Robert A. Anders, Edward Gabrielson, Peter Illei, Jaroslaw Jedrych, Ludmila Danilova and Joel Sunshine of Johns Hopkins. Other authors were from the Hospital Universitario Puerta de Hierro in Madrid, Spain; McGill University Health Center in Montreal, Canada; Institut du Thorax Curie-Montsouris in Paris, France; Aberdeen Royal Infirmary in the United Kingdom; Bristol Myers Squibb in Princeton, New Jersey; and Queen’s University in Kingston, Canada.

    The study was supported by Bristol Myers Squibb, Ono Pharmaceutical Company Ltd., the Bloomberg~Kimmel Institute for Cancer Immunotherapy, The Mark Foundation for Cancer Research and the National Institutes of Health (grant R01 CA142779).

    Deutsch is named on a patent for system and method for annotating pathology images to predict patient outcome (U.S. Provisional Patent Application 63/313,548, filed in Feb. 2022). Taube receives support for this study from Bristol Myers Squibb; receives consulting fees from AstraZeneca, Bristol Myers Squibb, Merck and Roche; participates on advisory boards from AstraZeneca; and is named on a patent for a machine learning algorithm for irPRC. These relationships are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

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  • Cancer Research Institute to Honor Dr. Ananda Goldrath with 2023 Alt Award

    Cancer Research Institute to Honor Dr. Ananda Goldrath with 2023 Alt Award

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    Newswise — New York, October 27, 2023

    The Cancer Research Institute (CRI), a nonprofit organization dedicated to harnessing the immune system’s power to control and potentially cure all cancers, will honor Dr. Ananda Goldrath, Executive Vice President and Director, Allen Institute for Immunology with the Frederick W. Alt Award for New Discoveries in Immunology. Dr. Goldrath will receive the award at the 2023 CRI Annual Awards Dinner on Monday, November 6, in New York City.

    The Frederick W. Alt award is designated specifically for former CRI postdoctoral fellows to honor their contribution towards research that has had an outsized impact in the field of immunology, either in academia or industry.

    The award is named after CRI Scientific Advisory Council member Frederick W. Alt, PhD (Boston Children’s Hospital & Harvard Medical School). Dr. Alt has empowered many emerging, promising scientists in his career, and has made several monumental contributions within the field of immunology.

    “The Cancer Research Institute has been supporting the training of young scientists and nurturing careers for decades,” says Dr. Goldrath. “CRI funded my training and research as a fellow and then again when I started my own lab. CRI funds helped us carry out some of our earliest experiments that led to key insights into how to induce ‘memory’ T cells that provide protective immunity and kill tumor cells. To receive the CRI 2023 Frederick W. Alt award for New Discoveries in Immunology is a thrilling honor and reflects the hard work and creativity of many brilliant trainees I have had the privilege of working with over the course of my career.”

    Dr. Goldrath has made many critical contributions to the field of immunology. Notably, her lab has revealed a mechanistic understanding of the creation and maintenance of long-lived protective immunity. She is extremely active in the larger science and immunology space, as a member of the American Academy of Arts and Sciences, a Pew Scholar, a Leukemia and Lymphoma Society Fellow, and a member of the Immunological Genome Project.

    Additionally, Dr. Goldrath recently joined the Allen Institute for Immunology after nearly two decades at the University of California San Diego where she was a Tata Chancellor’s Professor in the School of Biological Sciences in the Molecular Biology Department and Co-Director of the Program in Immunology.

    “Dr. Goldrath’s contributions to the field of immunology epitomize the sort of scientific excellence that CRI seeks in its most exceptional scientists,” says CRI CEO and Director of Scientific Affairs Jill O’Donnell-Tormey, PhD. “Her research on memory T cells has provided valuable insight on how to manipulate the immune system to deliver long lasting immunity against infection and cancer. Such discoveries are not only significant for the immunology field, but they benefit us all.”

    CRI is proud to honor Dr. Goldrath with the 2023 Fredrick W. Alt award for New Discoveries in Immunology. The discoveries she has made, and the knowledge she has passed on to scientists that have worked in her lab, go directly towards our goal of creating a world immune to cancer.

    About the Cancer Research Institute

    The Cancer Research Institute (CRI), established in 1953, is the preeminent U.S. nonprofit organization dedicated exclusively to saving more lives by fueling the discovery and development of powerful immunotherapies for all cancers. Guided by a world-renowned Scientific Advisory Council that includes four Nobel laureates and 33 members of the National Academy of Sciences, CRI has invested over $517 million in support of research conducted by immunologists and tumor immunologists at the world’s leading medical centers and universities and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to cancerresearch.org.

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    Cancer Research Institute

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  • Find-and-Replace Genome Editing with CRISPR: A Promising Therapeutic Strategy

    Find-and-Replace Genome Editing with CRISPR: A Promising Therapeutic Strategy

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    Newswise — Severe Combined Immunodeficiencies (SCIDs) are a group of debilitating primary immunodeficiency disorders, primarily caused by genetic mutations that disrupt T-cell development. SCID can also affect B-cell and natural killer cell function and counts. Left untreated, SCID proves fatal within the first year of life. The conventional treatment for SCID patients involves allogeneic hematopoietic stem cell transplantation (HSCT), but the challenges of finding compatible donors and potential complications like graft-versus-host disease (GVHD) pose significant hurdles in this approach.

    A groundbreaking solution has emerged with the advent of genome editing (GE), particularly using CRISPR-Cas9 technology. This cutting-edge gene therapy research offers hope for many genetic disorders such as SCID. The CRISPR-Cas9 system creates site-specific double-strand breaks in the DNA, allowing for precise gene editing. The repair process can either disrupt a specific gene or correct it, potentially targeting nearly any gene in the genome. This development opens the door to therapeutic interventions for a wide range of genomic diseases.

    One promising genome-editing approach, CRISPR-Cas9 Homology-directed repair (HDR)-mediated GE, offers the potential for precise gene insertion. In certain subtypes of SCID, an alternative to HSCT can involve conventional CRISPR-Cas9 HDR-mediated gene insertion, but it carries inherent risks, especially in cases like RAG2-SCID. RAG2 is nuclease involved in DNA cleavage during lymphocyte development, and CRISPR-Cas9 HDR-mediated gene insertion may lead to uncontrolled RAG2 nuclease activity and harmful structural variations.

    In response, researchers from Bar-Ilan University in Israel propose a novel replacement strategy, termed GE x HDR 2.0: Find and Replace. This approach, outlined in a paper published today in Nature Communications, combines CRISPR-Cas9-mediated genome editing with recombinant adeno-associated serotype 6 (rAAV6) DNA donor vectors to precisely replace the RAG2 coding sequence while preserving regulatory elements. This strategy can be applied also to other genes with hot spot regions for disease-causing mutations.

    Dr. Ayal Hendel, of Bar-Ilan University’s Goodman Faculty of Life Sciences, emphasized, “Our innovation hinges on a crucial insight: to efficiently trigger CRISPR-Cas9 HDR-mediated GE for precise coding sequence replacement, it’s essential to separate the distal homology arm from the cleavage site and align it with the sequence immediately downstream of the segment needing replacement. In this process, elongating the distal homology arm length in the donor is of paramount importance. By preserving endogenous regulatory elements and intronic sequences, our approach faithfully reproduces natural gene expression levels, thus reducing the associated risks of unregulated gene expression. This groundbreaking technique, which involves replacing entire coding sequences or exons while retaining critical regulatory elements, brings hope to patients with RAG2-SCID and holds promise for the treatment of various other genetic disorders.”

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  • Brain Immune Cell to Neuron Conversion Aids Post-Stroke Mouse Recovery.

    Brain Immune Cell to Neuron Conversion Aids Post-Stroke Mouse Recovery.

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    Newswise — Fukuoka, Japan – Researchers at Kyushu University have discovered that turning brain immune cells into neurons successfully restores brain function after stroke-like injury in mice. These findings, published on October 10 in PNAS, suggest that replenishing neurons from immune cells could be a promising avenue for treating stroke in humans.

    Stroke, and other cerebrovascular diseases, occur when blood flow to the brain is affected, causing damage to neurons. Recovery is often poor, with patients suffering from severe physical disabilities and cognitive problems. Worldwide, it’s one of the most common causes for needing long-term care.

    “When we get a cut or break a bone, our skin and bone cells can replicate to heal our body. But the neurons in our brain cannot easily regenerate, so the damage is often permanent,” says Professor Kinichi Nakashima, from Kyushu University’s Graduate School of Medical Sciences. “We therefore need to find new ways to replace lost neurons.”

    One possible strategy is to convert other cells in the brain into neurons. Here, the researchers focused on microglia, the main immune cells in the central nervous system. Microglia are tasked with removing damaged or dead cells in the brain, so after a stroke, they move towards the site of injury and replicate quickly.

    “Microglia are abundant and exactly in the place we need them, so they are an ideal target for conversion,” says first author, Dr. Takashi Irie from Kyushu University Hospital.

    In prior research, the team demonstrated that they could induce microglia to develop into neurons in the brains of healthy mice. Now, Dr. Irie and Professor Nakashima, along with Lecturer Taito Matsuda and Professor Noriko Isobe from Kyushu University Graduate School of Medical Sciences, showed that this strategy of replacing neurons also works in injured brains and contributes to brain recovery.

    To conduct the study, the researchers caused a stroke-like injury in mice by temporarily blocking the right middle cerebral artery – a major blood vessel in the brain that is commonly associated with stroke in humans. A week later, the researchers examined the mice and found that they had difficulties in motor function and had a marked loss of neurons in a brain region known as the striatum. This part of the brain is involved in decision making, action planning and motor coordination.

    The researchers then used a lentivirus to insert DNA into microglial cells at the site of the injury. The DNA held instructions for producing NeuroD1, a protein that induces neuronal conversion. Over the subsequent weeks, the infected cells began developing into neurons and the areas of the brain with neuron loss decreased. By eight weeks, the new induced neurons had successfully integrated into the brain’s circuits.

    At only three weeks post-infection, the mice showed improved motor function in behavioral tests. These improvements were lost when the researchers removed the new induced neurons, providing strong evidence that the newly converted neurons directly contributed to recovery.

    “These results are very promising. The next step is to test whether NeuroD1 is also effective at converting human microglia into neurons and confirm that our method of inserting genes into the microglial cells is safe,” says Professor Nakashima.

    Furthermore, the treatment was conducted in mice in the acute phase after stroke, when microglia were migrating to and replicating at the site of injury. Therefore, the researchers also plan to see if recovery is also possible in mice at a later, chronic phase.

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    Kyushu University

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  • MD Anderson Research Highlights: ESMO 2023 Special Edition

    MD Anderson Research Highlights: ESMO 2023 Special Edition

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    ABSTRACTS: LBA71, 1088MO, 95MO, LBA48, 1082O, 1085O, LBA34, 243MO

    Newswise — MADRID ― The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recent basic, translational and clinical cancer research from MD Anderson experts.

    This special edition features upcoming oral presentations by MD Anderson researchers at the 2023 European Society for Medical Oncology (ESMO) Congress focused on clinical advances across a variety of cancer types. Highlights include a combination strategy for EGFR-mutant metastatic lung cancer, updated results for a Phase II study on immunotherapy for skin cancer, a promising drug for bile duct cancer, pre-surgical treatment options for resectable melanoma, concurrent intrathecal and intravenous treatment for leptomeningeal disease, a triplet combination for melanoma brain metastases, promising results for an antibody drug conjugate targeting HER2, and the option to eliminate surgery for a subset of breast cancer patients. More information on ESMO content from MD Anderson can be found at MDAnderson.org/ESMO.

    In addition to the studies summarized below, forthcoming press releases will feature the following late-breaking and oral presentations:

    • Results from the Phase III CheckMate 77T study evaluating neoadjuvant nivolumab plus chemotherapy vs. neoadjuvant placebo plus chemotherapy followed by surgery and adjuvant nivolumab for untreated, resectable stage II-IIIB non-small cell lung cancer (Abstract LBA1)
    • Results from the Phase III DUO-E trial for newly diagnosed advanced or recurrent endometrial cancer (Abstract LBA41)
    • Results from the Phase III THOR study on erdafitinib vs. pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer (Abstract 2359O)
    • Subgroups from the Phase III THOR study on erdafitinib vs. chemotherapy in patients with advanced or metastatic urothelial cancer with select FGFR alterations (Abstract 2362MO) 

    Combination treatment prolongs survival in patients with EGFR-mutant lung cancer (Abstract LBA71)  
    Osimertinib, an EGFR inhibitor, is the current standard first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC), yet there is a need to identify improved treatments to enhance its initial efficacy. In the randomized Phase II RAMOSE trial, researchers led by Xiuning Le, M.D., Ph.D., found combining osimertintib with ramucirumab, an anti-VEGF treatment, significantly prolonged progression-free survival (PFS). The median PFS was 24.8 months in the combination arm compared to 15.6 months for those who received osimertintib alone. The combination also demonstrated a favorable safety profile. This study suggests osimertinib plus ramucirumab should be considered as a first-line treatment option for patients with EGFR-mutant metastatic NSCLC. Le will present the updated findings on October 21.

    Pre-surgical immunotherapy improves patient outcomes in advanced operable cutaneous squamous cell carcinoma (Abstract 1088MO) Patients with cutaneous squamous cell carcinoma (CSCC), the second most common form of skin cancer, typically present with early-stage disease that can be treated with surgery alone, though a subset with more advanced disease will require radiation in addition to surgery. In a one year follow-up to a multicenter Phase II study led by Neil D. Gross, M.D., neoadjuvant (pre-surgical) immunotherapy given to patients with advanced resectable CSCC demonstrated favorable survival outcomes with a median follow-up duration of 18.7 months. The study included 79 participants treated with neoadjuvant cemiplimab followed by curative-intent surgery. Based on treatment response, patients were offered up to 48 weeks of adjuvant cemiplimab, radiation therapy or observation only. Estimated 12-month event-free survival was 89%. Notably, none of the 40 patients with a pathological complete response (pCR) experienced recurrence. The results indicate that neoadjuvant cemiplimab followed by surgery is a viable treatment option for advanced, operable CSCC. A Phase III trial is planned to test this novel approach. Gross will present updated findings on Oct. 21.

    Tinengotinib delivers promising efficacy in patients with advanced cholangiocarcinoma (Abstract 95MO) Current FGFR inhibitor (FGFRi) therapies for patients with refractory or relapsed cholangiocarcinoma (CCA), or bile duct cancer, can lead to secondary FGFR2 mutations and treatment resistance. To address this, researchers led by Milind Javle, M.D., evaluated the efficacy and safety of tinengotinib, a next-generation FGFR2 inhibitor with unique target binding to overcome acquired resistance mutations. This Phase II trial enrolled patients who had received at least one prior line of chemotherapy, including those with prior FGFRi therapy. Patients with FGFR2 kinase domain mutations had the best overall response rate (ORR) at 44%. The ORR in patients with FGFR2-altered CCA was 29% and the disease control rate was 90%. For patients with prior FGFRi treatment, the ORR was 31%. The findings suggest tinengotinib may have a potential role in treating CCA patients with FGFR2 fusions, including those with prior FGFRi treatment. Researchers have launched the Phase III study of tinengotinib to further investigate this therapy. Javle will present the findings on Oct. 21.

    Perioperative immunotherapy improved outcomes in patients with late-stage melanoma (Abstract LBA48) 
    Patients with advanced melanoma face a significant risk of relapse even after surgery. Adding immunotherapy to surgery is considered more effective than surgery alone, but the proper timing of treatment is still unclear. In a follow-up analysis of a Phase II study led by Sapna Patel, M.D., researchers found neoadjuvant (pre-surgery) plus adjuvant (post-surgery) pembrolizumab lowered the chance of disease recurrence, progression or death, compared to adjuvant pembrolizumab alone for patients with stage IIIB-IV melanoma. Among those who had surgery and were evaluable for response, more than half had a major pathological response, which includes pathologic complete and near complete responses. These results suggest that perioperative (pre- and post-surgical) pembrolizumab should be considered when treating late-stage operable melanoma. Patel will present the updated findings on Oct. 23.  

    Intrathecal and intravenous immunotherapy improves survival in patients with leptomeningeal disease (Abstract 1082O) Leptomeningeal disease (LMD) occurs when cancer cells from tumors migrate into the cerebrospinal fluid (CSF) and leptomeninges, part of the lining of the brain and spinal cord. LMD can be challenging to diagnose and treat, and patients face poor survival rates. A recent proof-of-concept study showed that intrathecal (IT) nivolumab, which is administered directly into the CSF, along with intravenous (IV) immunotherapy helped improve survival in patients with LMD. Building upon this, Isabella Glitza Oliva, M.D., Ph.D., and colleagues continued the combination therapy in an IT dose expansion study. The median overall survival (OS) was 7.5 months, with a landmark OS rate of 68%, 54% and 35% at 3, 6 and 12 months, respectively. This study demonstrates the safety and efficacy of this combination of IT and IV therapy among 50 patients treated, confirming its feasibility and supporting ongoing clinical evaluation to further improve outcomes in this underserved patient population. Glitza Oliva will present updated clinical outcomes on Oct. 23.

    Triplet combination is safe and demonstrates clinical benefit in patients with refractory melanoma brain metastases (Abstract 1085O) While many patients with melanoma brain metastases (MBM) respond well to immune checkpoint blockade, many fail to respond or subsequently develop resistance, leaving them with limited systemic treatment options and a poor prognosis. In this Phase II study,a  research led by Elizabeth Burton examined the safety and efficacy of atezolizumab, bevacizumab and cobimetinib in 20 patients with treatment refractory MBM. The intracranial (IC) response rate and IC benefit rate were 38% and 53%, respectively. Safety was consistent with expectations, with 18 patients experiencing treatment-related adverse events (TRAEs) and 7 (35%) experiencing grade 3/4 TRAEs. Although the median PFS was 1.8 months, the median OS was 9.3 months. Eleven patients (55%) received treatment beyond progression, including stereotactic radiosurgery, after evaluation by MD Anderson’s multidisciplinary Brain Metastasis Clinic. These results, which highlight the tolerability of the combination, merit further clinical evaluation and underscore the importance of integrating multidisciplinary care into the evaluation of novel therapeutic strategies in this patient population. Burton will present updated findings on Oct. 23.

    Primary analysis of Phase II data of trastuzumab deruxtecan continues to show promising signals (Abstract LBA34) Trastuzumab deruxtecan (T-DXd), an antibody drug conjugate targeting HER2, has been approved for use in HER2-positive breast cancer, gastric cancer and HER2-mutant lung cancer. In the DESTINY-PanTumor02 study led by Funda Meric-Bernstam, M.D., T-DXd also showed potential as a treatment option in several other cancers, especially gynecological cancers. The objective response rate (ORR) across all patients was 37.1% with a duration of response of 11.3 months, but among patients with the highest levels of HER2 expression, ORR was 61.3% with a duration of 22.1 months. These data support the potential role of T-DXd as a tumor-agnostic therapy for patients with hard-to-treat HER2-expressing solid tumors that currently have limited treatment options. Interim data from this trial were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. Meric-Bernstam will present the primary analysis on Oct. 23.

    Eliminating surgery in select breast cancer patients shows low risk of cancer recurrence (Abstract 243MO)
    Approximately 60% of early-stage triple-negative and HER2-positive breast cancers have a positive response to chemotherapy. An exceptional response to chemotherapy is a strong indicator of a favorable prognosis and can be accurately confirmed through a minimally invasive image-guided vacuum-assisted core biopsy (VACB). In a Phase II trial led by Henry Kuerer, M.D., Ph.D., 50 patients underwent a VACB after completing chemotherapy. Previous reports of this research showed no breast cancer recurrence within two years. VACB identified a complete absence of cancer in 31 patients and, over three years, there were no recurrences in the same breast. The three-year disease-free survival and overall survival rates were both 100%. This study suggests that, for carefully selected breast cancer patients, avoiding surgery carries a minimal risk of disease recurrence. Further investigation and clinical trials are essential to validate this approach. Kuerer will present the three-year findings on Oct. 23.

     

    – 30 –

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