Influence of B cell or plasma cell-targeted CAR-T cell therapy on humoral immunity and vaccine immunogenicity: The HICAR study

Influence of B cell or plasma cell-targeted CAR-T cell therapy on humoral immunity and vaccine immunogenicity: The HICAR study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Influence of B cell or plasma cell-targeted CAR-T cell therapy on humoral immunity and vaccine immunogenicity: The HICAR study Joshua Hill, Stosh Ozog, Elizabeth Krantz, Karyn Tindbaek, Julian Munoz, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7061163/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Humoral immune-related adverse events, including hypogammaglobulinemia and B cell depletion, pose long-term infection risks after chimeric antigen receptor T cell therapy (CARTx) for hematologic malignancies. This prospective study evaluated the kinetics of pathogen-specific humoral immunity prior to and up to a year after CARTx targeting CD19 and CD20 (B cells) or BCMA (plasma cells) in 100 and 28 individuals, respectively. Antibodies were tested for 12 vaccine-preventable pathogens and using comprehensive high-throughput antibody profiling. A subset of 72 participants were evaluated for post-CARTx vaccine responses. Pathogen-specific humoral immunity did not significantly change after CD19- and CD20-targeted CARTx, but these individuals lacked seroprotective antibodies for up to one-third of routine vaccine-preventable pathogens. BCMA-CARTx recipients had a modest but non-significant increase in pathogen-specific humoral immunity after CARTx but still lacked seroprotective antibodies for nearly half of tested vaccine-preventable pathogens. Pre-vaccination B cell count ≥20 cells/μL was the main predictor of vaccine response. Health sciences/Medical research/Outcomes research Biological sciences/Immunology/Vaccines Biological sciences/Cancer/Cancer therapy/Cancer immunotherapy CAR-T cell therapy immunotherapy immunity immune reconstitution vaccination B cell malignancy Full Text Additional Declarations Yes there is potential Competing Interest. A.J.C. reports advising and consultancy for Sebia, Janssen Pharmaceuticals, BMS, Sanofi, HopeAI, Adaptive Biotechnologies, Abbvie, Kite/Arcellx and research funding from Janssen Pharmaceuticals, BMS, Juno/Celgene, Sanofi, Regeneron, IGM BIosciences, Nektar, Harpoon, Caelum, Opna Bio, and Karyopharm. D.J.G. reports advising for Juno Therapeutics, Seattle Genetics, Janssen Pharmaceuticals, Bristol-Myer Squibb, GlaxoSmithKline, Ensoma and Legend Biotech and research funding from Juno Therapeutics, Seattle Genetics, Janssen Pharmaceuticals, Bristol-Myers Squibb, SpringWorks Therapeutics, Sanofi, AstraZeneca and Cellectar Biosciences. J.G. reports consultancy for Bristol Myers Squibbs, Sobi, Legend Biotech, Janssen, Kite Pharma, MorphoSys and research funding from Sobi, Juno Therapeutics, Celgene, Angiocrine Bioscience, Faron Pharmaceuticals, CARGO Therapeutics, CytoAgents B.G.T. reports consultancy for Proteios Technology and research funding from Mustang Bio and BMS/Celgene. R.A.G. reports royalties from BMS related to patents in the CAR T cell field. C.J.T. reports advising for Caribou Biosciences, T-CURX, Myeloid Therapeutics, ArsenalBio, Cargo Therapeutics, Celgene/BMS Cell Therapy, Differentia Bio, eGlint, IQVIA, research funding from Juno Therapeutics/BMS, Nektar Therapeutics, 10X Genomics, Genscript, Kite/Gilead, Umoja Biopharma and consultancy for Prescient Therapeutics, Century Therapeutics, Boxer Capital, Novartis, Merck Sharp and Dohme, and Abbvie. J.A.H. reports consultancy for Moderna, Allovir, Gilead, Takeda, CSL Behring, Karius, Geovax, and Sanofi and research funding from Gilead, Takeda, Merck, Geovax, and Sanofi. All other authors deny any competing interests. Supplementary Files HICARSupplementFinal.pdf Supplemental Material Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7061163","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":484928216,"identity":"dc0b784d-8457-43a1-a52f-dfdd6e201ac5","order_by":0,"name":"Joshua 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Karyopharm.\r\n\r\nD.J.G. reports advising for Juno Therapeutics, Seattle Genetics, Janssen Pharmaceuticals, Bristol-Myer Squibb, GlaxoSmithKline, Ensoma and Legend Biotech and research funding from Juno Therapeutics, Seattle Genetics, Janssen Pharmaceuticals, Bristol-Myers Squibb, SpringWorks Therapeutics, Sanofi, AstraZeneca and Cellectar Biosciences. \r\n \r\nJ.G. reports consultancy for Bristol Myers Squibbs, Sobi, Legend Biotech, Janssen, Kite Pharma, MorphoSys and research funding from Sobi, Juno Therapeutics, Celgene, Angiocrine Bioscience, Faron Pharmaceuticals, CARGO Therapeutics, CytoAgents \r\n\r\nB.G.T. reports consultancy for Proteios Technology and research funding from Mustang Bio and BMS/Celgene.\r\n \r\nR.A.G. reports royalties from BMS related to patents in the CAR T cell field.\r\n\r\nC.J.T. reports advising for Caribou Biosciences, T-CURX, Myeloid Therapeutics, ArsenalBio, Cargo Therapeutics, Celgene/BMS Cell Therapy, Differentia Bio, eGlint, IQVIA, research funding 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This prospective study evaluated the kinetics of pathogen-specific humoral immunity prior to and up to a year after CARTx targeting CD19 and CD20 (B cells) or BCMA (plasma cells) in 100 and 28 individuals, respectively. Antibodies were tested for 12 vaccine-preventable pathogens and using comprehensive high-throughput antibody profiling. A subset of 72 participants were evaluated for post-CARTx vaccine responses. Pathogen-specific humoral immunity did not significantly change after CD19- and CD20-targeted CARTx, but these individuals lacked seroprotective antibodies for up to one-third of routine vaccine-preventable pathogens. BCMA-CARTx recipients had a modest but non-significant increase in pathogen-specific humoral immunity after CARTx but still lacked seroprotective antibodies for nearly half of tested vaccine-preventable pathogens. 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