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小分子靶向药物联合 CAR-T 细胞疗法治疗血液系统淋巴瘤的潜力

英文原题:Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas.

查看英文原题

Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas.

PubMed 2026/04/01(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
Tang W、Yu S
单位
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.China
文献类型
综述
期刊
Frontiers in immunology2026
原文标识
PubMed 41993181 · DOI 10.3389/fimmu.2026.1792910