Mardiana Sherly, Lai Junyun, House Imran Geoffrey, Beavis Paul Andrew, Darcy Phillip Kevin
Cancer Immunology Program Peter MacCallum Cancer Centre Melbourne VIC Australia.
Sir Peter MacCallum Department of Oncology The University of Melbourne Parkville VIC Australia.
Clin Transl Immunology. 2019 May 5;8(5):e1046. doi: 10.1002/cti2.1046. eCollection 2019.
Adoptive cellular therapy involving genetic modification of T cells with chimeric antigen receptor (CAR) transgene offers a promising strategy to broaden the efficacy of this approach for the effective treatment of cancer. Although remarkable antitumor responses have been observed following CAR T-cell therapy in a subset of B-cell malignancies, this has yet to be extended in the context of solid cancers. A number of promising strategies involving reprogramming the tumor microenvironment, increasing the specificity and safety of gene-modified T cells and harnessing the endogenous immune response have been tested in preclinical models that may have a significant impact in patients with solid cancers. This review will discuss these exciting new developments and the challenges that must be overcome to deliver a more sustained and potent therapeutic response.
采用嵌合抗原受体（CAR）转基因对T细胞进行基因改造的过继性细胞疗法，为拓宽该方法有效治疗癌症的疗效提供了一种有前景的策略。尽管在一部分B细胞恶性肿瘤患者接受CAR T细胞治疗后观察到了显著的抗肿瘤反应，但在实体癌背景下尚未得到推广。在临床前模型中已经测试了一些有前景的策略，包括重新编程肿瘤微环境、提高基因改造T细胞的特异性和安全性以及利用内源性免疫反应，这些策略可能对实体癌患者产生重大影响。本综述将讨论这些令人兴奋的新进展以及为实现更持久、有效的治疗反应必须克服的挑战。
