肿瘤细胞治疗研究
英文原题：Adoptive Cellular Therapy for Multiple Myeloma Using CAR- and TCR-Transgenic T Cells: Response and Resistance.
Adoptive Cellular Therapy for Multiple Myeloma Using CAR- and TCR-Transgenic T Cells: Response and Resistance.
尽管治疗方法有了显著改善，多发性骨髓瘤（MM）在很大程度上仍无法治愈。
尽管治疗方法有了显著改善，多发性骨髓瘤（MM）在很大程度上仍无法治愈。然而，免疫治疗尤其是基于T细胞的疗法最近开创了复发和难治性疾病的治疗格局。靶向骨髓瘤细胞上的B细胞成熟抗原（BCMA）已被证明不仅通过抗体衍生的构建体，而且通过过继性细胞疗法都具有高度有效性。嵌合抗原受体（CAR）转基因T细胞在重度预处理患者中导致深度缓解，尽管大多不持久，但副作用可控。过继性T细胞转移的范围涵盖具有多种特异性的合成CAR以及目前尚不太成熟的基于T细胞受体（TCR）的个性化策略。在这篇综述中，我们希望聚焦于CAR和TCR转基因T细胞在MM中的治疗特征，包括疗效和安全性，以及这些新型疗法未来可能具有的潜力。使用转基因T细胞的ACT才刚刚进入临床试验，需要各种工程策略来优化T细胞反应以克服治疗耐药机制。我们希望概述目前工程化CAR和TCR-T细胞的成功，但也讨论挑战，包括MM逃避T细胞治疗的耐药机制，并指出可能的新策略。
Despite the substantial improvement of therapeutic approaches, multiple myeloma (MM) remains mostly incurable. However, immunotherapeutic and especially T cell-based approaches pioneered the therapeutic landscape for relapsed and refractory disease recently. Targeting B-cell maturation antigen (BCMA) on myeloma cells has been demonstrated to be highly effective not only by antibody-derived constructs but also by adoptive cellular therapies. Chimeric antigen receptor (CAR)-transgenic T cells lead to deep, albeit mostly not durable responses with manageable side-effects in intensively pretreated patients. The spectrum of adoptive T cell-transfer covers synthetic CARs with diverse specificities as well as currently less well-established T cell receptor (TCR)-based personalized strategies. In this review, we want to focus on treatment characteristics including efficacy and safety of CAR- and TCR-transgenic T cells in MM as well as the future potential these novel therapies may have. ACT with transgenic T cells has only entered clinical trials and various engineering strategies for optimization of T cell responses are necessary to overcome therapy resistance mechanisms. We want to outline the current success in engineering CAR- and TCR-T cells, but also discuss challenges including resistance mechanisms of MM for evading T cell therapy and point out possible novel strategies.
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