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小分子化合物增强血液系统恶性肿瘤的 CAR-T 细胞疗法。

Small-Molecule Compounds Boost CAR-T Cell Therapy in Hematological Malignancies.

机构信息

First Center Clinic College of Tianjin Medical University, Tianjin, 300192, China.

Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, China.

出版信息

Curr Treat Options Oncol. 2023 Mar;24(3):184-211. doi: 10.1007/s11864-023-01049-4. Epub 2023 Jan 26.

Abstract

Although chimeric antigen receptor T cell immunotherapy has been successfully applied in patients with hematological malignancies, several obstacles still need to be overcome, such as high relapse rates and side effects. Overcoming the limitations of CAR-T cell therapy and boosting the efficacy of CAR-T cell therapy are urgent issues that must be addressed. The exploration of small-molecule compounds in combination with CAR-T cell therapies has achieved promising success in pre-clinical and clinical studies in recent years. Protein kinase inhibitors, demethylating drugs, HDAC inhibitors, PI3K inhibitors, immunomodulatory drugs, Akt inhibitors, mTOR inhibitors, and Bcl-2 inhibitors exhibited potential synergy in combination with CAR-T cell therapy. In this review, we will discuss the recent application of these combination therapies for improved outcomes of CAR-T cell therapy.

摘要

虽然嵌合抗原受体 T 细胞免疫疗法已成功应用于血液系统恶性肿瘤患者,但仍有几个障碍需要克服,如高复发率和副作用。克服 CAR-T 细胞治疗的局限性和提高 CAR-T 细胞治疗的疗效是亟待解决的问题。近年来,小分子化合物与 CAR-T 细胞疗法联合应用的探索在临床前和临床研究中取得了可喜的成功。蛋白激酶抑制剂、去甲基化药物、HDAC 抑制剂、PI3K 抑制剂、免疫调节剂、Akt 抑制剂、mTOR 抑制剂和 Bcl-2 抑制剂与 CAR-T 细胞治疗联合应用具有潜在的协同作用。本文将讨论这些联合治疗方法在改善 CAR-T 细胞治疗效果方面的最新应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/671e/9992085/bd5d210b9c55/11864_2023_1049_Fig1_HTML.jpg

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