CD19嵌合抗原受体修饰的T细胞治疗血液系统恶性肿瘤

CD19 chimeric antigen receptor T cell therapy for haematological malignancies

Summary
T cells can be redirected to recognize tumour antigens by genetic modification to express a chimeric antigen receptor (CAR). These consist of antibody-derived antigen-binding regions linked to T cell signalling elements. CD19 is an ideal target because it is expressed on most B cell malignancies as well as normal B cells but not on other cell types, restricting any ‘on target, off tumour’ toxicity to B cell depletion. Recent clinical studies involving CD19 CAR-directed T cells have shown unprecedented responses in a range of B cell malignancies, even in patients with chemorefractory relapse. Durable responses have been achieved, although the persistence of modified T cells may be limited. This therapy is not without toxicity, however. Cytokine release syndrome and neurotoxicity appear to be frequent but are treatable and reversible. CAR T cell therapy holds the promise of a tailored cellular therapy, which can form memory and be adapted to the tumour microenvironment. This review will provide a perspective on the currently available data, as well as on future developments in the field.
Keywords: T lymphocytes, immunotherapy, gene transfer, cellular therapies.


CD19嵌合抗原受体修饰的T细胞治疗血液系统恶性肿瘤
T细胞通过基因改造能够表达嵌合抗原受体，用来识别肿瘤抗原。这些CAR由抗体来源的抗原结合区域与T细胞信号分子相结合。CD19是一个理想的靶标，因为它在大多数B淋巴恶性细胞表面和正常B淋巴细胞表面表达，而不在其他细胞表面表达，限制任何“靶向非肿瘤”毒性对B 细胞造成消耗。最近涉及到CD19 CAR-T细胞的临床试验，在一系列B淋巴细胞恶性肿瘤病人中甚至是耐药复发性病人中，已经展现出了前所未有的疗效。虽然修饰后的T细胞的持久性可能被限制，但是持久的有效性已经能够实现。这个治疗不是没有毒性。细胞因子的释放综合征和神经毒性似乎是常见的，但是是可以治疗的和可逆转的。CAR-T细胞治疗是量身定制细胞治疗的希望，能够适应肿瘤微环境和形成记忆。这篇综述依据目前可用的数据提供了一个视角和在这个领域将来的发展。
关键词：淋巴细胞，免疫治疗，基因转移，细胞治疗。