Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Expert Rev Hematol. 2020 May;13(5):533-543. doi: 10.1080/17474086.2020.1753501. Epub 2020 Apr 27.
: The field of immunotherapy has witnessed considerable progress over the last two decades. Beginning with the ability to conceptualize CAR T cell therapy as immunotherapeutic approach, to effortlessly genetically modifying T cells, we have now reached the stage of mass production for clinical needs, all within less than quarter of a century.: CAR T cell therapy has been tremendously successful in acute leukemia patients, specifically even in relapsed/refractory disease states. However, similar success is yet to be realized in other malignancies. This review article covers the challenges encountered with the current CD19-targeted CARs, as well as specific obstacles faced by adoptive therapy in solid tumors. It also discusses various strategies to counteract these problems.: CD19-directed trials in the past decade have exposed vulnerabilities in the current CAR T cell design, particularly concerning safety aspects, antigen escape, and T cell persistence. Building on these lessons and factoring in the unique challenges associated with immunotherapy in solid tumors will help generate CARs designed for future trials. Also, research related to the production of allogeneic CAR T cell products will boost the patient reach of this unique technology and possibly reduce financial burden.
: 在过去的二十年中，免疫疗法领域取得了相当大的进展。从能够将 CAR T 细胞疗法概念化为免疫治疗方法，到轻松地对 T 细胞进行基因修饰，我们现在已经能够满足临床需求进行大规模生产，所有这些都在不到四分之一的世纪内完成。: CAR T 细胞疗法在急性白血病患者中取得了巨大成功，特别是在复发/难治性疾病状态下。然而，在其他恶性肿瘤中尚未取得类似的成功。本文综述了当前针对 CD19 的 CAR 所面临的挑战，以及过继性治疗在实体瘤中面临的具体障碍。还讨论了各种克服这些问题的策略。: 在过去十年中针对 CD19 的试验揭示了当前 CAR T 细胞设计的脆弱性，特别是在安全性、抗原逃逸和 T 细胞持久性方面。基于这些经验教训，并考虑到实体瘤免疫治疗所特有的挑战，将有助于生成用于未来试验的 CAR。此外，与异体 CAR T 细胞产品生产相关的研究将提高这项独特技术的患者受益面，并可能减轻经济负担。
