Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19
James N Kochenderfer, Wyndham H Wilson, John E Janik, Mark E Dudley, Maryalice Stetler-Stevenson, Steven A Feldman, Irina Maric, Mark Raffeld, Debbie-Ann N Nathan, Brock J Lanier, Richard A Morgan, Steven A Rosenberg, James N Kochenderfer, Wyndham H Wilson, John E Janik, Mark E Dudley, Maryalice Stetler-Stevenson, Steven A Feldman, Irina Maric, Mark Raffeld, Debbie-Ann N Nathan, Brock J Lanier, Richard A Morgan, Steven A Rosenberg
Abstract
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.
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Source: PubMed