CAR-T细胞免疫治疗：发展犹如从普通道路到高速公路

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CAR T-cell immunotherapy: The path from the by-road to the freeway?

Abstract

Chimeric antigen receptors are genetically encoded artificial fusion molecules that can re-program the specificity of pe**heral blood polyclonal T-cells against a selected cell surface target. Unparallelled clinical efficacy has recently been demonstrated using this approach to treat patients with refractory B-cell malignancy. However, the approach is technically challenging and can elicit severe toxicity in patients. Moreover, solid tumours have largely proven refractory to this approach. In this review, we describe the important structural features of CARs and how this may influence function. Emerging clinical experience is summarized in both solid tumours and haematological malignancies. Finally, we consider the particular challenges imposed by solid tumours to the successful development of CAR T-cell immunotherapy, together with a number of innovative strategies that have been developed in an effort to reverse the balance in favour of therapeutic benefit.

KEYWORDS:

Cancer; Chimeric antigen receptor; Immunotherapy; Solid tumours; T-cells

CAR-T细胞免疫治疗：发展犹如从普通道路到高速公路

摘要：

嵌合抗原受体是基因编码的人工融合分子，能够重新编程外周血多克隆T细胞的特异性有选择对抗细胞表面靶点。优质的临床疗效已经在使用这种方法治疗难治性B细胞恶性肿瘤中体现出来。然而，该方法在技术上仍然具有挑战性，并且会引起患者严重的毒副反应。此外，实体肿瘤的治疗也很大程度证实了这种方法的难度。在这篇综述中，我们描述了CARs重要的结构特征，和这些特征是如何影响功能的。总结了在实体瘤和血液系统恶性肿瘤一些CAR-T治疗的新的临床经验。最后，我们认为使用CAR-T免疫治疗实体肿瘤面临着特殊的挑战，以及讨论一些有利于治疗的新的策略的开发。

关键词：癌；嵌合抗原受体；免疫治疗；肿瘤；T细胞

出自爱康得生物技术