Althafar Ziyad M
Department of Medical Laboratories Sciences, College of Applied Medical Sciences in Alquwayiyah, Shaqra University, Riyadh, Saudi Arabia.
Front Pharmacol. 2025 Jun 12;16:1614325. doi: 10.3389/fphar.2025.1614325. eCollection 2025.
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.
实体瘤约占人类癌症的90%,由于抗原异质性、免疫抑制微环境以及传统药物疗法的可及性有限,带来了独特的挑战。免疫疗法,尤其是工程化免疫细胞疗法,利用免疫与肿瘤的相互作用,为实体恶性肿瘤提供了新的药理学策略。基因工程通过优化其靶向和效应功能,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、肿瘤浸润淋巴细胞(TILs)、自然杀伤细胞和CAR巨噬细胞。临床上,TIL递送在晚期黑色素瘤中显示出显著疗效,lifileucel作为首个用于实体瘤的TIL疗法获得了美国食品药品监督管理局(FDA)的批准。正在进行的试验进一步探索这些方法,在克服免疫抑制障碍方面显示出有前景的结果。然而,挑战依然存在,包括优化联合疗法、简化生产以实现现成可用以及减轻药物毒性。本综述总结了实体瘤工程化免疫细胞疗法的最新进展,强调了其药理学机制、临床疗效和转化潜力。通过解决当前的障碍,如增强肿瘤穿透性和最小化不良反应,本文概述了将这些疗法优化为肿瘤学中安全、有效的药理学工具的未来方向。
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