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 evaluates 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 are tested for 12 vaccine-preventable pathogens and using comprehensive high-throughput antibody profiling. A subset of 72 participants are evaluated for post-CARTx vaccine responses. Here, we show pathogen-specific humoral immunity does not significantly change after CD19-, CD20-, or BCMA-targeted CAR-T cell therapy (CARTx). However, seroprotective antibodies are absent for up to one-third of routine vaccine-preventable pathogens in CD19- and CD20-CARTx recipients and for nearly half of vaccine-preventable pathogens in BCMA-CARTx recipients by one-year post-CARTx. Pre-vaccination B cell count is the main predictor of vaccine response.
Data availability
Comprehensive individual-level data generated in this study contain human participant information and, therefore, are not publicly available due to ethical and legal restrictions, including participant privacy protections and the terms of informed consent. Access to the minimum necessary de-identified dataset required to reproduce all analyses is available via controlled access through Fred Hutchinson Cancer Center’s data governance processes. Requests will be subject to institutional review and require submission of (i) a brief research proposal, (ii) documentation of IRB/ethics approval or exemption as applicable, and (iii) execution of an appropriate data use agreement. Requests may be initiated by contacting the corresponding author (jahill3@fredhutch.org) after publication. The authors will make their best efforts to provide the requested information within 3 months of the request. Source data are provided with this paper.
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Acknowledgements
The authors would like to acknowledge Mr. Rob Burton and Sunfire Biotechnologies for conducting and interpreting the S. pneumococcal multiplexed opsonophagocytosis assay testing. The authors thank Dr. Jeffrey Cohen (National Institute of Allergy and Infectious Diseases) for guidance on VZV antibody testing. Funding for this work was provided by the National Institutes of Health/National Cancer Institute (5U01CA247548 to J.A.H., NCI T32 CA009351 to S.O.). This research was supported by the Immune Monitoring Shared Resource, RRID:SCR_022615, of the Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium (P30 CA015704). The authors would also like to acknowledge Jacob Keane-Candib, Joyce Maalouf, and Atif Bhatti for help with study implementation.
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J.A.H. conceptualized and oversaw the study. Participant recruitment, enrollment, sample processing, and testing were conducted by K.T., W.L., J.M., and C.C. Flow cytometry and analysis were conducted by S.P. and J.B. VirScan library preparation and analysis were performed by K.Y. and T.S.-A. Analysis, data visualization, and interpretation were performed by E.M.K., S.D., S.O., and J.A.H. Preparation of the paper, figures, tables, and supplementary figures was performed by S.O., E.M.K., S.D., and J.A.H. Additional facilitation of participant enrollment and intellectual input was provided by A.J.C., D.J.G., J.G., B.G.T., R.A.G., M.S., M.Bl., M.Bo., and C.J.T. Edits and revisions were provided by all authors.
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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-Myers 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, and 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 others deny any competing interests.
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Ozog, S., Krantz, E.M., Tindbaek, K. et al. Influence of B cell-lineage targeted CAR-T cell therapy on humoral immunity and vaccine-induced antibody response. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71473-1
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DOI: https://doi.org/10.1038/s41467-026-71473-1
