T cells engineered to express chimeric antigen receptors (CARs) with tumor specificity have shown remarkable success in treating patients with hematologic malignancies and revitalized the field of adoptive cell therapy. However, realizing broader therapeutic applications of CAR-T cells necessitates engineering approaches on multiple levels to enhance efficacy and safety. Particularly, solid tumors present unique challenges due to the biological complexity of the solid-tumor microenvironment (TME). In this review, we highlight recent strategies to improve CAR-T cell therapy by engineering (1) the CAR protein, (2) T cells, and (3) the interaction between T cells and other components in the TME.

经工程改造以表达具有肿瘤特异性的嵌合抗原受体 (CARs) 的 T 细胞在治疗血液系统恶性肿瘤患者方面取得了显著成功，并振兴了过继细胞治疗领域。然而，实现 CAR-T 细胞更广泛的治疗应用需要多层次的工程方法来提高疗效和安全性。特别是，由于实体瘤微环境 (TME) 的生物学复杂性，实体瘤提出了独特的挑战。在这篇综述中，我们重点介绍了最近通过改造（1）CAR蛋白、（2）T细胞和（3）T细胞与TME中其他成分之间的相互作用来改善CAR-T细胞治疗的策略。