淋巴恶性肿瘤免疫治疗新方法

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Novel immunotherapies in lymphoid malignancies

Abstract

The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of ** and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE®) antibody, is now approved for the treatment of **s with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens.

淋巴恶性肿瘤免疫治疗新方法

靶向CD20单克隆抗体立普妥单抗在恶性淋巴瘤中的治疗成功，为开发免疫系统治疗提供了证据。自从FDA在1997年批准了立普妥单抗，一些新的利用T细胞靶向对抗癌细胞的策略也出现了。为了体现出这些新的免疫治疗途径的前景，FDA最近对三种不同机制的新治疗方法赋予了“重要技术突破”的称号。首先，嵌合抗原受体修饰的T细胞（CAR-T）治疗方案对成人和儿童复发或难治性急性淋巴白血病（ALL）的治疗表现出了希望。第二，blinatumomab，双特异性T细胞衔接器（BiTE®）抗体药物，现在被批准用于治疗成人费城染色体缺失型复发和/或者难治性记性B淋巴细胞白血病。最后一个，是单克隆抗体立普妥，针对PD-1免疫检查点受体具有高亲和力，被用于治疗霍奇金淋巴瘤治疗后失败的自体干细胞移植和药物brentuximab vedotin治疗。在这里，我们回顾了这三种不同的免疫治疗平台的背景和发展过程，了解每种治疗方案的作用机制,从而促进科学的提高，评估目前的临床知识，疗效和安全性。此外,我们还讨论了将来的一些治疗策略，通过加强改造、生物标志物的选择、以机制为基础的联合治疗方案来提高这些免疫疗法的疗效。

出自爱康得生物技术