Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):570-578. doi: 10.1182/hematology.2020002547.
T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed the paradigm of treatment for many patients with relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T cell therapy in both the autologous and allogeneic settings, including practical, logistical, and toxicity issues. Given these concerns, there is a rapidly growing interest in natural killer cells as alternative vehicles for CAR engineering, given their unique biological features and their established safety profile in the allogeneic setting. Other immune effector cells, such as invariant natural killer T cells, γδ T cells, and macrophages, are attracting interest as well and eventually may be added to the repertoire of engineered cell therapies against cancer. The pace of these developments will undoubtedly benefit from multiple innovative technologies, such as the CRISPR-Cas gene editing system, which offers great potential to enhance the natural ability of immune effector cells to eliminate refractory cancers.
嵌合抗原受体 (CAR) 修饰的 T 细胞彻底改变了细胞治疗领域，改变了许多复发或难治性 B 细胞恶性肿瘤患者的治疗模式。尽管取得了这些进展，但 CAR-T 细胞疗法在自体和同种异体环境中都存在局限性，包括实际问题、后勤问题和毒性问题。鉴于这些担忧，鉴于自然杀伤细胞 (NK 细胞) 的独特生物学特性及其在同种异体环境中的既定安全性，人们对其作为 CAR 工程的替代载体越来越感兴趣。其他免疫效应细胞，如不变自然杀伤 T 细胞 (iNKT 细胞)、γδ T 细胞和巨噬细胞，也引起了人们的兴趣，最终可能会被添加到针对癌症的工程细胞治疗方案中。这些发展的步伐无疑将受益于多种创新技术，如 CRISPR-Cas 基因编辑系统，该系统为增强免疫效应细胞消除难治性癌症的天然能力提供了巨大潜力。
