Secondino Simona, Canino Costanza, Alaimo Domiziana, Muzzana Marta, Galli Giulia, Borgetto Sabrina, Basso Sabrina, Bagnarino Jessica, Pulvirenti Chiara, Comoli Patrizia, Pedrazzoli Paolo
Oncology Department, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
Department of Internal Medicine and Medical Therapy, University of Pavia, 27100 Pavia, Italy.
Cancers (Basel). 2023 Jul 19;15(14):3667. doi: 10.3390/cancers15143667.
In the past years cancer treatments have drastically changed, mainly due to the development of immune checkpoint inhibitors capable of immune modulation in vivo, thus providing major clinical benefit in a number of malignancies. Simultaneously, considerable technical refinements have opened new prospects for the development of immune cell-based medicinal products and unprecedented success with chimeric antigen receptor (CAR)-T cells targeting B-cell hematologic malignancies has been obtained. However, T cell therapies introduced and performed in the field of solid tumors have produced so far only limited responses in selected patient populations. This standstill is attributable to the difficulty in identifying target antigens which are homogeneously expressed by all tumor cells while absent from normal tissues, and the limited T cell persistence and proliferation in a hostile tumor microenvironment that favors immune escape. Replicating the results observed in hematology is a major scientific challenge in solid tumors, and ongoing translational and clinical research is focused on obtaining insight into the mechanisms of tumor recognition and evasion, and how to improve the efficacy of cellular therapies, also combining them with immune checkpoint inhibitors or other agents targeting either the cancer cell or the tumor environment. This paper provides an overview of current adaptive T cell therapy approaches in solid tumors, the research performed to increase their efficacy and safety, and results from ongoing clinical trials.
在过去几年中，癌症治疗发生了巨大变化，这主要归功于能够在体内进行免疫调节的免疫检查点抑制剂的发展，从而在多种恶性肿瘤中带来了重大临床益处。与此同时，技术上的显著改进为基于免疫细胞的药物产品开发开辟了新前景，并且在靶向B细胞血液系统恶性肿瘤的嵌合抗原受体（CAR）-T细胞方面取得了前所未有的成功。然而，到目前为止在实体瘤领域引入并实施的T细胞疗法仅在部分患者群体中产生了有限的反应。这种停滞归因于难以识别所有肿瘤细胞均均匀表达而正常组织中不存在的靶抗原，以及在有利于免疫逃逸的恶劣肿瘤微环境中T细胞的持久性和增殖受限。在实体瘤中复制血液学中观察到的结果是一项重大科学挑战，目前正在进行的转化研究和临床研究专注于深入了解肿瘤识别和逃逸机制，以及如何提高细胞疗法的疗效，还包括将它们与免疫检查点抑制剂或其他靶向癌细胞或肿瘤环境的药物联合使用。本文概述了实体瘤中当前的适应性T细胞治疗方法、为提高其疗效和安全性所开展的研究以及正在进行的临床试验结果。
