Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells produced lasting remissions in the treatment of advanced, so far refractory B-cell malignancies; however, the elimination of solid tumors remains so far elusive. The low efficacy of CAR T cells is thought to be due to the immune-repressive milieu within the tumor lesion, predominantly mediated by transforming growth factor-β (TGF-β) that represses effector T-cell activities and drives differentiation towards regulatory T cells (Tregs). Seeking to boost antitumor immunity, TGF-β is currently targeted by different means in pre-clinical studies. While a recent clinical trial showed the utility of shielding CAR T cells from TGF-β repression, further strategies in counteracting TGF-β in the adoptive cell therapy warrant exploration. We here discuss the most recent advances in the field and draw future developments to make CAR T-cell therapy more potent in the treatment of solid cancer.

中文翻译：

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嵌合抗原受体设计用于在实体瘤的过继T细胞治疗中克服转化生长因子-β介导的抑制作用。

嵌合抗原受体（CAR）工程化的T细胞的过继细胞疗法在晚期，迄今难治性B细胞恶性肿瘤的治疗中产生持久的缓解；然而，到目前为止，消除实体瘤仍然是遥不可及的。CAR T细胞的低效率被认为是由于肿瘤病变内的免疫抑制环境所致，主要是由转化生长因子-β（TGF-β）介导的，该因子抑制效应子T细胞活性并推动向调节性T细胞的分化（Tregs）。为了提高抗肿瘤免疫力，TGF-β目前在临床前研究中以不同方式靶向。尽管最近的一项临床试验显示了将CAR T细胞从TGF-β抑制中屏蔽的效用，但在过继细胞疗法中对抗TGF-β的其他策略值得探索。