Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies.
Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies.
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DOI：
10.1007/s12185-013-1479-5
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发表时间：
2014-04
影响因子：
2.1
通讯作者：
Brentjens R
中科院分区：
文献类型：
--
作者：
Davila ML;Bouhassira DC;Park JH;Curran KJ;Smith EL;Pegram HJ;Brentjens R
利用嵌合抗原受体（CARs）对自体T细胞进行基因修饰是基因工程治疗血液系统恶性肿瘤的一个突破。通过靶向CD19抗原，我们已经在大量预处理和化疗难治性B细胞急性淋巴细胞白血病（BALL）患者中证明了强大和快速的抗白血病活性。我们在成人中证明了深度分子缓解的快速诱导，最近在一个涉及B-ALL儿童的病例报告中证实了这一点。与治疗B-ALL的结果相反，慢性淋巴细胞白血病（CLL）或其他非霍奇金淋巴瘤（NHL）患者的结果更为温和。我们回顾了针对B-ALL和CLL的临床试验经验，推测了不同结果的可能原因，并提出了针对CLL或其他惰性NHL的CAR - T细胞治疗的潜在优化。最后，我们讨论了CAR - T细胞治疗多发性骨髓瘤和急性髓性白血病的临床前发展和临床转化潜力。我们强调针对这些预后不良的血液恶性肿瘤的潜在风险和益处。
The genetic modification of autologous T cells with chimeric antigen receptors (CARs) represents a breakthrough for gene engineering as a cancer therapy for hematologic malignancies. By targeting the CD19 antigen, we have demonstrated robust and rapid anti-leukemia activity in patients with heavily pre-treated and chemotherapy-refractory B cell acute lymphoblastic leukemia (BALL). We demonstrated rapid induction of deep molecular remissions in adults, which has been recently confirmed in a case report involving a child with B-ALL. In contrast to the results when treating B-ALL, outcomes have been more modest in patients with chronic lymphocytic leukemia (CLL) or other non-hodgkin’s lymphoma (NHL). We review the clinical trial experience targeting B-ALL and CLL and speculate on the possible reasons for the different outcomes and propose potential optimization to CAR T cell therapy when targeting CLL or other indolent NHL. Lastly, we discuss the pre-clinical development and potential for clinical translation for using CAR T cells against multiple myeloma and acute myeloid leukemia. We highlight the potential risks and benefits by targeting these poor outcome hematologic malignancies.