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

被引:1037
作者
Kochenderfer, James N. [1 ,2 ]
Wilson, Wyndham H. [3 ]
Janik, John E. [3 ]
Dudley, Mark E. [2 ]
Stetler-Stevenson, Maryalice [4 ]
Feldman, Steven A. [2 ]
Maric, Irina [1 ]
Raffeld, Mark [4 ]
Nathan, Debbie-Ann N. [2 ]
Lanier, Brock J. [2 ]
Morgan, Richard A. [2 ]
Rosenberg, Steven A. [2 ]
机构
[1] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA
[2] NCI, Surg Branch, Bethesda, MD 20892 USA
[3] NCI, Metab Branch, Bethesda, MD 20892 USA
[4] NCI, Pathol Lab, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
CHIMERIC ANTIGEN RECEPTOR; HUMAN BONE-MARROW; IN-VIVO; ADOPTIVE IMMUNOTHERAPY; ANTITUMOR-ACTIVITY; LYMPHOCYTES; ANTIBODY; DIFFERENTIATION; PERSISTENCE; EFFICACY;
D O I
10.1182/blood-2010-04-281931
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Blood.2010;116(20):4099-4102)
引用
收藏
页码:4099 / 4102
页数:4
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