Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19
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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DOI：
10.1182/blood-2010-04-281931
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发表时间：
2010-11-18
期刊：
影响因子：
20.3
通讯作者：
Rosenberg, Steven A.
中科院分区：
文献类型：
--
作者：
Kochenderfer, James N.;Wilson, Wyndham H.;Rosenberg, Steven A.
遗传修饰的T细胞的连续转移是用于产生抗肿瘤免疫应答的有吸引力的方法。我们治疗了一名晚期滤泡性淋巴瘤患者，给予了一种准备性化疗方案，然后是自体T细胞，经基因工程改造后表达一种识别B细胞抗原CD 19的嵌合抗原受体（CAR）。患者的淋巴瘤经历了戏剧性的消退，并且在输注抗CD 19-CAR转导的T细胞后，B细胞前体被选择性地从患者的骨髓中消除。尽管其他血细胞计数迅速恢复，但在抗CD 19-CAR转导的T细胞输注后至少39周内不存在血液B细胞。与B系细胞的根除一致，治疗后血清免疫球蛋白降低至非常低的水平。B系细胞的延长和选择性消除不能归因于患者接受的化疗，表明B系细胞的抗原特异性根除。表达抗CD 19-CAR的T细胞的连续转移是治疗B细胞恶性肿瘤的一种有前途的新方法。本研究在www.clinicaltrials.gov注册为#NCT 00924326。（Blood.2010;116（20）：4099-4102）
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)