학술논문
Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies.
Document Type
Academic Journal
Author
Walti CS; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Krantz EM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Maalouf J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Boonyaratanakornkit J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Department of Medicine, University of Washington, Seattle, Washington, USA.; Keane-Candib J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Joncas-Schronce L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Stevens-Ayers T; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Dasgupta S; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Taylor JJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Hirayama AV; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Bar M; Department of Medicine, University of Washington, Seattle, Washington, USA.; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Gardner RA; Clinical Research Division, and.; Seattle Children's Hospital, Seattle, Washington, USA.; Cowan AJ; Department of Medicine, University of Washington, Seattle, Washington, USA.; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Green DJ; Department of Medicine, University of Washington, Seattle, Washington, USA.; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Boeckh MJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Department of Medicine, University of Washington, Seattle, Washington, USA.; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Maloney DG; Department of Medicine, University of Washington, Seattle, Washington, USA.; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Turtle CJ; Department of Medicine, University of Washington, Seattle, Washington, USA.; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Hill JA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Department of Medicine, University of Washington, Seattle, Washington, USA.; Clinical Research Division, and.; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Source
Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
Subject
Language
English
Abstract
BACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay. The primary outcome was the proportion of participants with IgG levels above a threshold correlated with seroprotection for vaccine-preventable infections.RESULTSWe enrolled 65 children and adults a median of 20 months after CD19- (n = 54) or BCMA- (n = 11) CAR-T cell therapy. Among 30 adults without IgG replacement therapy (IGRT) in the prior 16 weeks, 27 (90%) had hypogammaglobulinemia. These individuals had seroprotection to a median of 67% (IQR, 59%-73%) of tested infections. Proportions of participants with seroprotection per pathogen were comparable to population-based studies, but most individuals lacked seroprotection to specific pathogens. Compared with CD19-CAR-T cell recipients, BCMA-CAR-T cell recipients were half as likely to have seroprotection (prevalence ratio, 0.47; 95% CI, 0.18-1.25) and had fewer pathogen-specific epitope hits (mean difference, -90 epitope hits; 95% CI, -157 to -22).CONCLUSIONSeroprotection for vaccine-preventable infections in adult CD19-CAR-T cell recipients was comparable to the general population. BCMA-CAR-T cell recipients had fewer pathogen-specific antibodies. Deficits in both groups support the need for vaccine and immunoglobulin replacement therapy studies.FUNDINGSwiss National Science Foundation (Early Postdoc Mobility grant P2BSP3_188162), NIH/National Cancer Institute (NIH/NCI) (U01CA247548 and P01CA018029), NIH/NCI Cancer Center Support Grants (P30CA0087-48 and P30CA015704-44), American Society for Transplantation and Cellular Therapy, and Juno Therapeutics/BMS.