Srour Samer A, Akin Serkan
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medical Oncology, Hacettepe University Cancer Institute, Hacettepe University, Ankara, Turkey.
J Immunother Precis Oncol. 2022 Dec 28;6(1):19-30. doi: 10.36401/JIPO-22-7. eCollection 2023 Feb.
Chimeric antigen receptor (CAR) T-cell therapy is the new standard treatment for various indications in patients with advanced hematologic malignancies. Despite the several preclinical and early phase clinical trials, the overall clinical experience has been disappointing when applying this innovative therapy in solid tumors. The failure of CAR T-cell therapy and its limited antitumor activity in solid tumors have been attributed to several mechanisms, including tumor antigen heterogeneity, the hostile tumor microenvironment and poor trafficking of CAR T cells into tumor sites, and the unacceptable toxicities in some settings, among others. However, remarkable improvements have been made in understanding many of these failure mechanisms for which several emerging novel approaches are being applied to overcome these challenges. In this review, after a brief historic background for immunotherapy in solid tumors, we highlight the recent developments achieved in CAR T-cell designs, summarize completed clinical trials, and discuss current challenges facing CAR T-cell therapy and the suggested strategies to overcome these barriers.
嵌合抗原受体（CAR）T细胞疗法是晚期血液系统恶性肿瘤患者多种适应症的新标准治疗方法。尽管进行了多项临床前和早期临床试验，但在实体瘤中应用这种创新疗法时，总体临床经验并不理想。CAR T细胞疗法在实体瘤中的失败及其有限的抗肿瘤活性归因于多种机制，包括肿瘤抗原异质性、恶劣的肿瘤微环境、CAR T细胞向肿瘤部位的迁移不佳以及在某些情况下不可接受的毒性等。然而，在理解许多这些失败机制方面已经取得了显著进展，为此正在应用一些新兴的新方法来克服这些挑战。在本综述中，在简要介绍实体瘤免疫治疗的历史背景后，我们重点介绍了CAR T细胞设计方面的最新进展，总结了已完成的临床试验，并讨论了CAR T细胞疗法目前面临的挑战以及克服这些障碍的建议策略。
