Ghorashian Sara, Pule Martin, Amrolia Persis
Molecular and Cellular Immunology Unit, Institute of Child Health, University College London, London, UK.
Br J Haematol. 2015 May;169(4):463-78. doi: 10.1111/bjh.13340. Epub 2015 Mar 5.
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.
通过基因改造使T细胞表达嵌合抗原受体（CAR），可使其重新定向识别肿瘤抗原。这些嵌合抗原受体由与T细胞信号元件相连的抗体衍生抗原结合区域组成。CD19是一个理想的靶点，因为它在大多数B细胞恶性肿瘤以及正常B细胞上表达，但在其他细胞类型上不表达，从而将任何“靶向肿瘤外”的毒性限制为B细胞耗竭。最近涉及CD19 CAR定向T细胞的临床研究表明，在一系列B细胞恶性肿瘤中都出现了前所未有的反应，即使是在化疗难治性复发的患者中也是如此。尽管修饰后的T细胞的持久性可能有限，但已经实现了持久反应。然而，这种疗法并非没有毒性。细胞因子释放综合征和神经毒性似乎很常见，但可以治疗且可逆。CAR T细胞疗法有望成为一种定制的细胞疗法，它可以形成记忆并适应肿瘤微环境。本综述将对目前可用的数据以及该领域的未来发展提供一个视角。
