CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas.
Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas.
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作为B细胞非霍奇金淋巴瘤的传统一线标准治疗,R-CHOP化疗方案面临约30%-40%的患者进展为复发/难治性疾病的问题。以BTK抑制剂和Bcl-2抑制剂为代表的小分子靶向药物以及CAR-T 细胞治疗在淋巴瘤治疗中取得了突破性成果,但仍面临单药疗效有限、耐药复发和毒性反应等限制。为了克服单一治疗的不足,联合治疗策略已成为研究热点。本综述系统总结了目前小分子靶向药物与CAR-T 细胞治疗联合应用的临床前及早期临床疗效证据,并探讨了小分子靶向药物与CAR-T 细胞治疗联合应用的潜在协同机制,包括改善肿瘤微环境、增强CAR-T 细胞功能、提高肿瘤细胞对CAR-T 的敏感性、抑制耗竭以及降低毒性。该联合策略有望提高疗效并克服耐药,是未来复发/难治性淋巴瘤治疗极具前景的发展方向。同时,还需进一步深入研究以推动其临床转化与应用。
As the traditional first-line standard treatment of B-cell non-Hodgkin's lymphoma, the R-CHOP chemotherapy regimen faces the problem of about 30%-40% of patients progressing into relapsed or refractory disease. Small molecule targeted drugs and CAR-T cell therapy, represented by BTK inhibitors and Bcl-2 inhibitors have achieved breakthrough results in the treatment of lymphoma, but they still face restrictions such as limited single-drug efficacy, drug-resistant recurrence, and toxic reactions. In order to overcome the shortcomings of single therapy, combined treatment strategies have become a research hotspot. This review systematically summarizes the efficacy evidence of the current preclinical and early clinical combined treatment of small molecule targeted drugs and CAR-T cell therapy.
The potential synergistic mechanism of the joint application of small molecule targeted drugs and CAR-T cell therapy is discussed, including improving the tumor microenvironment, enhancing the function of CAR-T cells, improving the sensitivity of tumor cells to CAR-T, inhibiting exhaustion, and reducing toxicity.
This joint strategy is expected to improve the therapeutic effect and overcome drug resistance. It is a very promising development direction for the treatment of relapsed or refractory lymphoma in the future. At the same time, further in-depth research is needed to promote its clinical transformation and application.
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