Department of Oncology and Metabolism, University of Tabuk, Tabuk, Saudi Arabia.
School of Humanities, Natural & Social Sciences, New Uzbekistan University, 54 Mustaqillik Ave., 100007, Tashkent, Uzbekistan.
Med Oncol. 2023 Oct 1;40(11):313. doi: 10.1007/s12032-023-02191-7.
Treatment with chimeric antigen receptor (CAR) T cells indicated remarkable clinical responses with liquid cancers such as hematological malignancies; however, their therapeutic efficacy faced with many challenges in solid tumors due to severe toxicities, antigen evasion, restricted and limited tumor tissue trafficking and infiltration, and, more importantly, immunosuppressive tumor microenvironment (TME) factors that impair the CAR T-cell function adds support survival of cancer stem cells (CSCs), responsible for tumor recurrence and resistance to current cancer therapies. Therefore, in-depth identification of TME and development of more potent CAR platform targeting CSCs may overcome the raised challenges, as presented in this review. We also discuss recent stemness-based innovations in CAR T-cell production and engineering to improve their efficacy in vivo, and finally, we propose solutions and strategies such as oncolytic virus-based therapy and combination therapy to revive the function of CAR T-cell therapy, especially in TME of solid tumors in future.
嵌合抗原受体 (CAR) T 细胞治疗在血液恶性肿瘤等液体癌中表现出显著的临床反应；然而，由于严重的毒性、抗原逃逸、受限和有限的肿瘤组织运输和浸润，以及更重要的是抑制性肿瘤微环境 (TME) 因素，其在实体瘤中的治疗效果面临许多挑战，这些因素损害了 CAR T 细胞的功能，增加了癌症干细胞 (CSC) 的存活支持，导致肿瘤复发和对当前癌症治疗的耐药性。因此，正如本文所介绍的，深入了解 TME 并开发针对 CSCs 的更有效的 CAR 平台可能会克服这些挑战。我们还讨论了基于干细胞特性的 CAR T 细胞生产和工程学的最新创新，以提高其在体内的疗效，最后，我们提出了一些解决方案和策略，如溶瘤病毒治疗和联合治疗，以恢复 CAR T 细胞治疗的功能，特别是在未来的实体瘤 TME 中。
