Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeri...

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Published in:Blood 2010-11, Vol.116 (20), p.4099-4102
Main Authors: Kochenderfer, James N., Wilson, Wyndham H., Janik, John E., Dudley, Mark E., Stetler-Stevenson, Maryalice, Feldman, Steven A., Maric, Irina, Raffeld, Mark, Nathan, Debbie-Ann N., Lanier, Brock J., Morgan, Richard A., Rosenberg, Steven A.
Format: Article
Language:English
Subjects:
Antigens, CD19 - immunology
B-Lymphocytes - cytology
Cell Lineage - immunology
Gene Therapy
Genetic Engineering
Humans
Lymphocyte Depletion
Lymphoma - immunology
Lymphoma - therapy
Male
Receptors, Antigen - immunology
Remission Induction
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Transduction, Genetic
Transplantation, Autologous
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creator Kochenderfer, James N.
Wilson, Wyndham H.
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Rosenberg, Steven A.
description Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti–CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti–CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti–CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.
doi_str_mv 10.1182/blood-2010-04-281931
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source ScienceDirect®
subjects Antigens, CD19 - immunology
B-Lymphocytes - cytology
Cell Lineage - immunology
Gene Therapy
Genetic Engineering
Humans
Lymphocyte Depletion
Lymphoma - immunology
Lymphoma - therapy
Male
Receptors, Antigen - immunology
Remission Induction
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Transduction, Genetic
Transplantation, Autologous
title Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19
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