Li Hua, Zhao Yangbing
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-5156, USA.
Cancer Center, Chengdu Military General Hospital, Chengdu, 610083, China.
Protein Cell. 2017 Aug;8(8):573-589. doi: 10.1007/s13238-017-0411-9. Epub 2017 Apr 22.
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal-curing cancer with high safety, high efficacy, and low cost.
嵌合抗原受体（CAR）T细胞疗法是一种很有前景的癌症治疗方法，近年来发展迅速。然而，仍然存在一些重大挑战，包括精确的肿瘤靶向以避免脱靶或“靶向/肿瘤外”毒性、T细胞向实体瘤的充分浸润和迁移，以及T细胞在实体瘤的物理和生化屏障中的增殖和持久性。在这篇综述中，我们重点关注设计安全有效的CAR T细胞的主要挑战和策略，包括使用用于CAR和载体设计的新型前沿技术以提高安全性和疗效、进一步的T细胞修饰以克服肿瘤相关的免疫抑制，以及使用基因编辑技术来产生通用型CAR T细胞。所有这些努力都促进了CAR T细胞疗法的发展和演进，并朝着我们的最终目标迈进——以高安全性、高疗效和低成本治愈癌症。
