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实体瘤中适应性免疫效应疗法的发展。

Development of adaptive immune effector therapies in solid tumors.

机构信息

Cell Factory and Pediatric Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Institut Paoli-Calmettes, Aix-Marseille University, INSERM CBT 1409, Centre for Clinical Investigation in Biotherapy, Marseille, France.

出版信息

Ann Oncol. 2019 Nov 1;30(11):1740-1750. doi: 10.1093/annonc/mdz285.

Abstract

State-of-the-art treatment strategies have drastically ameliorated the outcome of patients affected by cancer. However, resistant and recurrent solid tumors are generally nonresponsive to conventional therapies. A central factor in the sequence of events that lead to cancer is an alteration in antitumor immune surveillance, which results in failure to recognize and eliminate the transformed tumor cell. A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of cancer provides the basis for improved therapies. Targeted strategies, such as T-cell therapy, not only generally spare normal tissues, but also use alternative antineoplastic mechanisms that synergize with other therapeutics. Despite encouraging success in hematologic malignancies, adaptive cellular therapies for solid tumors face unique challenges because of the immunosuppressive tumor microenvironment, and the hurdle of T-cell trafficking within scarcely accessible tumor sites. This review provides a brief overview of current cellular therapeutic strategies for solid tumors, research carried out to increase efficacy and safety, and results from ongoing clinical trials.

摘要

最先进的治疗策略极大地改善了癌症患者的预后。然而,耐药和复发性实体瘤通常对常规治疗无反应。导致癌症的一系列事件的一个核心因素是抗肿瘤免疫监视的改变,这导致无法识别和消除转化的肿瘤细胞。对免疫系统在癌症的发生和发展过程中的失调和逃逸有了更深入的了解,为改进治疗方法提供了基础。靶向策略,如 T 细胞疗法,不仅通常可以保护正常组织,而且还利用与其他疗法协同作用的替代抗肿瘤机制。尽管在血液恶性肿瘤方面取得了令人鼓舞的成功,但由于免疫抑制性肿瘤微环境以及 T 细胞在难以接近的肿瘤部位内迁移的障碍,实体瘤的适应性细胞疗法面临着独特的挑战。这篇综述简要概述了目前用于实体瘤的细胞治疗策略、为提高疗效和安全性而进行的研究以及正在进行的临床试验结果。

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