Search

Your search keyword '"Carla S Walti"' showing total 2 results
Start Over Author "Carla S Walti" Publisher american society for clinical investigation
2 results on '"Carla S Walti"'

1. Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies

Author

Carla S. Walti, Elizabeth M. Krantz, Joyce Maalouf, Jim Boonyaratanakornkit, Jacob Keane-Candib, Laurel Joncas-Schronce, Terry Stevens-Ayers, Sayan Dasgupta, Justin J. Taylor, Alexandre V. Hirayama, Merav Bar, Rebecca A. Gardner, Andrew J. Cowan, Damian J. Green, Michael J. Boeckh, David G. Maloney, Cameron J. Turtle, and Joshua A. Hill

Subjects
Infectious disease, Oncology, Medicine
Abstract

BACKGROUND Little is known about pathogen-specific humoral immunity after chimeric antigen receptor–modified T (CAR-T) cell therapy for B cell malignancies.METHODS We 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.RESULTS We 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).CONCLUSION Seroprotection 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.FUNDING Swiss 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.

Published
2021
Full Text
View/download PDF

2. Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies

Author

Alexandre V. Hirayama, Damian J. Green, Terry Stevens-Ayers, Joshua A. Hill, Andrew J. Cowan, Justin J. Taylor, Joyce Maalouf, Laurel Joncas-Schronce, Carla S Walti, Jacob Keane-Candib, Elizabeth M Krantz, Jim Boonyaratanakornkit, Michael Boeckh, Rebecca Gardner, Merav Bar, Cameron J. Turtle, David G. Maloney, and Sayan Dasgupta

Subjects
0301 basic medicine, Male, Cancer immunotherapy, Antibodies, Viral, Immunotherapy, Adoptive, Epitope, Cell therapy, 0302 clinical medicine, Agammaglobulinemia, Prospective Studies, Child, education.field_of_study, Infectious disease, Receptors, Chimeric Antigen, biology, General Medicine, Middle Aged, Antibodies, Bacterial, 3. Good health, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, Female, Antibody, Multiple Myeloma, Adult, Lymphoma, B-Cell, Adolescent, Population, Adaptive immunity, Antigens, CD19, Immunoglobulins, 03 medical and health sciences, Young Adult, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Vaccine-Preventable Diseases, medicine, Leukemia, B-Cell, Humans, B-Cell Maturation Antigen, education, B cell, Aged, business.industry, Cancer, Infant, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Immunity, Humoral, Transplantation, 030104 developmental biology, Cross-Sectional Studies, Immunoglobulin G, Immunology, Humoral immunity, biology.protein, Clinical Medicine, business
Abstract

BACKGROUND Little is known about pathogen-specific humoral immunity after chimeric antigen receptor–modified T (CAR-T) cell therapy for B cell malignancies. METHODS We 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. RESULTS We 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). CONCLUSION Seroprotection 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. FUNDING Swiss 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., In this prospective study, we investigated antibodies against vaccine-preventable infections and other pathogen-specific antibodies in individuals with remission after CAR-T cell therapy for B lineage malignancies.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results