Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building 2nd Floor, Room 2-140, Boston, MA 02215, USA.
Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building 2nd Floor, Room 2-140, Boston, MA 02215, USA.
Hematol Oncol Clin North Am. 2023 Dec;37(6):1149-1168. doi: 10.1016/j.hoc.2023.05.009. Epub 2023 Jun 21.
We review chimeric antigen receptor (CAR) T-cell therapy for solid tumors. We discuss patient selection factors and aspects of clinical management. We describe challenges including physical and molecular barriers to trafficking CAR-Ts, an immunosuppressive tumor microenvironment, and difficulty finding cell surface target antigens. The application of new approaches in synthetic biology and cellular engineering toward solid tumor CAR-Ts is described. Finally, we summarize reported and ongoing clinical trials of CAR-T therapies for select disease sites such as head and neck (including thyroid cancer), lung, central nervous system (glioblastoma, neuroblastoma, glioma), sarcoma, genitourinary (prostate, renal, bladder, kidney), breast and ovarian cancer.
我们回顾了嵌合抗原受体 (CAR) T 细胞疗法在实体瘤中的应用。我们讨论了患者选择因素和临床管理方面的问题。我们描述了包括 CAR-T 细胞运输的物理和分子障碍、免疫抑制性肿瘤微环境以及难以找到细胞表面靶抗原在内的挑战。还介绍了在合成生物学和细胞工程方面应用于实体瘤 CAR-T 细胞的新方法。最后,我们总结了报告和正在进行的 CAR-T 疗法临床试验,这些试验针对特定疾病部位,如头颈部(包括甲状腺癌)、肺、中枢神经系统(胶质母细胞瘤、神经母细胞瘤、脑胶质瘤)、肉瘤、泌尿生殖系统(前列腺、肾、膀胱、肾脏)、乳腺和卵巢癌。