Influence of B cell-lineage targeted CAR-T cell therapy on humoral immunity and vaccine-induced antibody response
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.
Authors
- Jim Boonyaratanakornkit (ORCID: https://orcid.org/0000-0001-5858-2662)
- Damian J. Green (ORCID: https://orcid.org/0000-0003-0477-1446)
- Jordan Gauthier (ORCID: https://orcid.org/0000-0002-5769-8409)
- Marie Bleakley (ORCID: https://orcid.org/0000-0002-7018-8702)
- Winnie Liu (ORCID: https://orcid.org/0000-0003-4127-860X)
- Stosh Ozog
- Brian G. Till (ORCID: https://orcid.org/0000-0002-4718-8288)
- Clementine Chalal
- Elizabeth M. Krantz
- Cameron J. Turtle (ORCID: https://orcid.org/0000-0002-4722-4461)
- Khaleel Yahya
- Terry Stevens-Ayers
- Julian Munoz
- Karyn Tindbaek
- Rebecca A. Gardner
- Andrew J. Cowan
- Mazyar Shadman
- Sara Pernikoff
- Joshua A. Hill
- Michael Boeckh
Institutions
- BC Cancer Agency (CA)
- Seattle Children's Hospital (US)
- The University of Sydney (AU)
- St. Jude Children's Research Hospital (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- University of Miami (US)
- University of Washington (US)
- Royal North Shore Hospital (AU)
- Fred Hutch Cancer Center (US)
- Sylvester Comprehensive Cancer Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-06
- DOI
- https://doi.org/10.1038/s41467-026-71473-1
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health