Hawkins Elizabeth R, D'Souza Reena R, Klampatsa Astero
Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
Biologics. 2021 Apr 14;15:95-105. doi: 10.2147/BTT.S291768. eCollection 2021.
Chimeric antigen receptor (CAR) T-cell therapy engineers T-cells to express a synthetic receptor which redirects effector function to the tumor, to improve efficacy and reduce toxicities associated with conventional treatments, such as radiotherapy and chemotherapy. This approach has proved effective in treating hematological malignancies; however, the same effects have not been observed in solid tumors. The immunosuppressive tumor microenvironment (TME) creates a significant barrier to solid tumor efficacy and reduces the anti-cancer activity of endogenous tumor-resident immune cells, enabling cancer progression. In recent years, researchers have attempted to enhance CAR T-cell function in the TME by engineering the cells to express various proteins alongside the CAR. Examples of this engineering include inducing CAR T-cells to secrete cytokines or express cytokine receptors to modulate the cytokine milieu of the TME. Alternatively, the CAR T-cell may secrete antibody-like proteins to target a range of tumor antigens. Collectively, these methods are termed armored CAR T-cell therapy, and in this review, we will discuss the range of armored CAR T-cell approaches which have been investigated to date.
嵌合抗原受体(CAR)T细胞疗法通过对T细胞进行工程改造,使其表达一种合成受体,该受体将效应功能重定向至肿瘤,以提高疗效并降低与放疗和化疗等传统治疗相关的毒性。这种方法已被证明在治疗血液系统恶性肿瘤方面有效;然而,在实体瘤中尚未观察到相同的效果。免疫抑制性肿瘤微环境(TME)对实体瘤疗效构成了重大障碍,并降低了内源性肿瘤驻留免疫细胞的抗癌活性,从而使癌症进展。近年来,研究人员试图通过对细胞进行工程改造,使其在表达CAR的同时表达各种蛋白质,来增强TME中CAR T细胞的功能。这种工程改造的例子包括诱导CAR T细胞分泌细胞因子或表达细胞因子受体,以调节TME的细胞因子环境。或者,CAR T细胞可以分泌抗体样蛋白来靶向一系列肿瘤抗原。总的来说,这些方法被称为武装CAR T细胞疗法,在本综述中,我们将讨论迄今为止已研究的一系列武装CAR T细胞方法。
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