重新编程肿瘤微环境以提高细胞的治疗

Reprogramming the tumor microenvironment to enhance adoptive cellular therapy.
Abstract
The frontiers of cancer immunotherapy are extending in terms of both the range of cancer types that can potentially be targeted and the types of therapeutics that are in clinical development. The use of adoptive cellular therapy (ACT) and its derivative, chimeric antigen receptor (CAR) T cells, is currently limited to hematological malignancies and immunogenic cancers such as melanoma and renal cell carcinoma. Although ACT utilizing ex vivo expanded tumor-infiltrating lymphocytes (TIL) or engineered CAR/TCR T cells have undergone clinical trials for other solid cancers, their efficacy to date has been limited. This may be due, in part, to the immunosuppressive nature of the tumor microenvironment. The development of novel combination approaches which target the immunosuppressive network engineered by tumors has raised the possibility of using ACT for a broader range of cancers. This review summarizes the potential of such strategies and outlines the clinical relevance of these observations.
Copyright © 2015. Published by Elsevier Ltd.
KEYWORDS:
Adoptive cellular therapy; Cancer; Chimeric antigen receptor; Immunosuppression; Immunotherapy
重新编程肿瘤微环境以提高细胞的治疗
摘要
最前沿的癌症免疫治疗得到扩展，体现在两方面，一是能够潜在靶向对抗的癌症的种类，二是临床治疗的方式。过继细胞治疗以及其衍生技术，嵌合抗原受体修饰的T细胞，目前仅限于血液系统恶性肿瘤和免疫原性肿瘤如黑色素瘤和肾细胞癌。虽然过继细胞治疗（ACT）体内使用扩大了肿瘤浸润淋巴细胞（TIL）的治疗，或者修饰过的CAR/TCR T细胞已经用于其他实体肿瘤的治疗，它们的有效性到目前为止还是有限的。这部分原因，可能是由于肿瘤微环境的免疫抑制性。靶向针对由肿瘤细胞改造过的免疫抑制网络的新型联合治疗方法的发展增加了使用ACT治疗更广泛癌症的可能性。这篇综述总结了这些策略的潜力，并概述了这些观察得到的临床相关性。
关键词：肿瘤；嵌合抗原受体；免疫抑制；免疫疗法
出自爱康得生物技术