Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Discov. 2021 Jan;11(1):45-58. doi: 10.1158/2159-8290.CD-20-0556. Epub 2020 Dec 4.
Chimeric antigen receptor (CAR) engineering of T cells has revolutionized the field of cellular therapy for the treatment of cancer. Despite this success, autologous CAR-T cells have recognized limitations that have led to the investigation of other immune effector cells as candidates for CAR modification. Recently, natural killer (NK) cells have emerged as safe and effective platforms for CAR engineering. In this article, we review the advantages, challenges, and preclinical and clinical research advances in CAR NK cell engineering for cancer immunotherapy. We also briefly consider the feasibility and potential benefits of applying other immune effector cells as vehicles for CAR expression. SIGNIFICANCE: CAR engineering can redirect the specificity of immune effector cells, converting them to a much more potent weapon to combat cancer cells. Expanding this strategy to immune effectors beyond conventional T lymphocytes could overcome some of the limitations of CAR T cells, paving the way for safer and more effective off-the-shelf cellular therapy products.
嵌合抗原受体 (CAR) 修饰 T 细胞在癌症的细胞治疗领域引发了变革。尽管取得了这些成功，但自体 CAR-T 细胞存在一些局限性，促使人们开始研究其他免疫效应细胞作为 CAR 修饰的候选细胞。最近，自然杀伤 (NK) 细胞作为 CAR 工程的安全有效平台已崭露头角。本文综述了 CAR-NK 细胞工程在癌症免疫治疗中的优势、挑战、临床前和临床研究进展。我们还简要考虑了将其他免疫效应细胞作为 CAR 表达载体的可行性和潜在获益。意义：CAR 工程可改变免疫效应细胞的特异性，将其转化为对抗癌细胞的更强大武器。将这一策略扩展到常规 T 淋巴细胞以外的免疫效应细胞，可能克服 CAR-T 细胞的一些局限性，为更安全、更有效的现成细胞治疗产品铺平道路。
