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利用细胞因子优化胃癌 CAR-T 细胞治疗:当前进展与创新策略

英文原题:Harnessing cytokines to optimize chimeric antigen receptor-T cell therapy for gastric cancer: Current advances and innovative strategies.

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Harnessing cytokines to optimize chimeric antigen receptor-T cell therapy for gastric cancer: Current advances and innovative strategies.

PubMed 2024/08/02(内容时间) Biomed Pharmacother

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中文摘要

大量胃癌(GC)患者对化疗和靶向治疗不敏感,且没有根治性手术的机会,因此免疫治疗可能为他们提供新的选择。嵌合抗原受体(CAR)-T细胞疗法具有特异性更高、杀伤力更强、疗效更持久的优势,未来有望用于GC。

然而,其在准确性、疗效和安全性方面仍面临诸多障碍。细胞因子可介导免疫细胞的迁移、增殖和存活,调节免疫反应的持续时间和强度,并参与CAR-T 细胞治疗中严重副作用的发生。特定细胞因子的表达水平与GC的发生、侵袭、转移和预后相关。细胞因子及其受体在CAR-T 细胞治疗中的应用已经出现,多种细胞因子及其受体有助于提高CAR-T 细胞的抗肿瘤能力。该治疗中大量存在的核心细胞因子包括趋化因子、白细胞介素(IL)、转化生长因子-(TGF-)和集落刺激因子(CSF)。

同时,研究人员已探索了治疗GC的联合疗法,若干应用于其他恶性肿瘤的方法也可作为参考。因此,本综述全面概述了细胞因子的生物学功能和临床意义,并总结了当前利用细胞因子优化GC的CAR-T 细胞治疗的进展和创新策略。

展开英文摘要原文

Enormous patients with gastric cancer (GC) are insensitive to chemotherapy and targeted therapy without the chance of radical surgery, so immunotherapy may supply a novel choice for them. Chimeric antigen receptor (CAR)-T cell therapy has the advantages of higher specificity, stronger lethality, and longer-lasting efficacy, and it has the potential for GC in the future.

However, its application still faces numerous obstacles in terms of accuracy, efficacy, and safety. Cytokines can mediate the migration, proliferation, and survival of immune cells, regulate the duration and strength of immune responses, and are involved in the occurrence of severe side effects in CAR-T cell therapy. The expression levels of specific cytokines are associated with the genesis, invasion, metastasis, and prognosis of GC.

Applications of cytokines and their receptors in CAR-T cell therapy have emerged, and various cytokines and their receptors have contributed to improving CAR-T cell anti-tumor capabilities. Large amounts of central cytokines in this therapy include chemokines, interleukins (ILs), transforming growth factor- (TGF- ), and colony-stimulating factors (CSFs). Meanwhile, researchers have explored the combination therapy in treating GC, and several approaches applied to other malignancies can also be considered as references.

Therefore, our review comprehensively outlines the biological functions and clinical significance of cytokines and summarizes current advances and innovative strategies for harnessing cytokines to optimize CAR-T cell therapy for GC.

论文信息

作者
Cheng Z、Cui X、Li S、Liang Y、Yang W、Ouyang J、Wei M、Yan Z
第一作者单位
Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.China
通讯作者单位
Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Electronic address: wenbin_yu2003@163.com.China
文献类型
综述
期刊
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2024 Sep
原文标识
PubMed 39096620 · DOI 10.1016/j.biopha.2024.117229