CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Secretory co-factors in next-generation cellular therapies for cancer.
Secretory co-factors in next-generation cellular therapies for cancer.
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自美国食品药品监督管理局批准嵌合抗原受体(CAR)T细胞治疗血液系统恶性肿瘤以来,研究人员已开发出多种“下一代”CAR-T 细胞,以改善其安全性、疗效和适用范围。尽管一些新策略前景良好,但将其用于实体瘤并控制细胞因子释放综合征、神经毒性等不良反应,仍具挑战。CAR-T 细胞可通过高度可扩展的基因工程技术制备。下一代CAR-T 细胞的一项主要开发策略,是在CAR基因的人工设计中整合有益的辅助因子,使细胞同时表达CAR和辅助因子。已有多种可分泌的CAR-T 辅助因子被报道,其疗效和毒性也已通过全身给药进行测试;因此,利用分泌型辅助因子的CAR-T 细胞可能接近临床应用。本文综述了已报道的多种可提高CAR-T 疗效、减轻不良事件的分泌型辅助因子,并讨论用于优化其获益的不同因子表达系统。
总体而言,将CAR-T 细胞与分泌型辅助因子结合,有望发展出适用于更广泛癌症类型的下一代CAR-T 疗法,并为更复杂的合成免疫治疗提供先进工具。
Since chimeric antigen receptor (CAR) T-cell therapies for hematologic malignancies were approved by the U. S. Food and Drug Administration, numerous "next-generation" CAR T cells have been developed to improve their safety, efficacy, and applicability. Although some of these novel therapeutic strategies are promising, it remains difficult to apply these therapies to solid tumors and to control adverse effects, such as cytokine release syndrome and neurotoxicity. CAR T cells are generated using highly scalable genetic engineering techniques.
One of the major strategies for producing next-generation CAR T cells involves the integration of useful co-factor(s) into the artificial genetic design of the CAR gene, resulting in next-generation CAR T cells that express both CAR and the co-factor(s). Many soluble co-factors have been reported for CAR T cells and their therapeutic effects and toxicity have been tested by systemic injection; therefore, CAR T cells harnessing secretory co-factors could be close to clinical application.
Here, we review the various secretory co-factors that have been reported to improve the therapeutic efficacy of CAR T cells and ameliorate adverse events.
In addition, we discuss the different co-factor expression systems that have been used to optimize their beneficial effects. Altogether, we demonstrate that combining CAR T cells with secretory co-factors will lead to next-generation CAR T-cell therapies that can be used against broader types of cancers and might provide advanced tools for more complicated synthetic immunotherapies.
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