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实体瘤的工程化免疫细胞治疗:药理学进展、临床结局与未来方向

英文原题:Engineered immune cell therapies for solid tumors: pharmacological advances, clinical outcomes, and future directions.

PubMed 2025/06/12(内容时间) Front Pharmacol Q1 · IF 5.4(JCR 2025)

研究概要

实体肿瘤约占人类癌症的90%,由于抗原异质性、免疫抑制微环境以及常规药物治疗的可及性有限,其治疗面临独特挑战。

中文摘要

实体肿瘤约占人类癌症的90%,由于抗原异质性、免疫抑制微环境及常规药物治疗的可及性有限,其治疗面临独特挑战。免疫疗法,特别是工程化免疫细胞疗法,利用免疫-肿瘤相互作用,为实体恶性肿瘤提供了新颖的药理学策略。基因工程通过优化靶向性和效应功能,增强了过继转移细胞,如T细胞受体疗法、嵌合抗原受体(CAR)-T细胞、TIL(肿瘤浸润淋巴细胞)(TILs)、NK 细胞及CAR-巨噬细胞。临床上,TIL输注在晚期黑色素瘤中显示出显著疗效,其中lifileucel作为首个针对实体肿瘤的TIL疗法获得美国FDA批准。正在进行的试验进一步探索这些方法,显示出在克服免疫抑制屏障方面的前景。然而,挑战依然存在,包括优化联合疗法、简化制造流程以实现即用型可及性,以及减轻药物毒性。本综述综合了工程化免疫细胞疗法在实体肿瘤中的最新进展,强调其药理学机制、临床疗效及转化潜力。通过解决当前障碍,如增强肿瘤穿透性和减少不良反应,本文概述了未来方向,以将这些疗法完善为肿瘤学中安全有效的药理学工具。

展开英文摘要原文

Solid tumors, accounting for around 90% of human cancers, present unique challenges due to antigen heterogeneity, immunosuppressive microenvironments, and limited accessibility for conventional pharmacotherapies. Immunotherapies, particularly engineered immune cell therapies, exploit the immune-tumor interplay, offering novel pharmacological strategies for solid malignancies. Genetic engineering enhances adoptively transferred cells, such as T cell receptor therapy, chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes (TILs), natural killer cells, and CAR-macrophages, by optimizing their targeting and effector functions. Clinically, TIL delivery has shown significant responses in advanced melanoma, with lifileucel gaining United States FDA approval as a pioneering TIL therapy for solid tumors. Ongoing trials further explore these approaches, revealing promising outcomes in overcoming immunosuppressive barriers. However, challenges persist, including optimizing combination therapies, streamlining manufacturing for off-the-shelf accessibility, and mitigating pharmacotoxicity. This review synthesizes recent advances in engineered immune cell therapies for solid tumors, emphasizing their pharmacological mechanisms, clinical efficacy, and translational potential. By addressing current hurdles, such as enhancing tumor penetration and minimizing adverse effects, this article outlines future directions to refine these therapies as safe, effective pharmacological tools in oncology.

论文信息

作者
Althafar ZM
单位
Department of Medical Laboratories Sciences, College of Applied Medical Sciences in Alquwayiyah, Shaqra University, Riyadh, Saudi Arabia.Saudi Arabia
文献类型
综述
期刊
Frontiers in pharmacology2025
原文标识
PubMed 40575784 · DOI 10.3389/fphar.2025.1614325