Center for Exploratory Research, Research and Development Group, Hitachi Ltd., Kobe, Japan.
Front Immunol. 2022 Aug 18;13:907022. doi: 10.3389/fimmu.2022.907022. eCollection 2022.
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.
自嵌合抗原受体 (CAR) T 细胞疗法被美国食品和药物管理局批准用于血液系统恶性肿瘤以来，已经开发出许多“下一代”CAR T 细胞来提高其安全性、疗效和适用性。尽管其中一些新的治疗策略很有前途，但仍然难以将这些疗法应用于实体瘤并控制不良反应，如细胞因子释放综合征和神经毒性。CAR T 细胞是使用高度可扩展的基因工程技术产生的。生产下一代 CAR T 细胞的主要策略之一是将有用的辅助因子整合到 CAR 基因的人工遗传设计中，从而产生表达 CAR 和辅助因子的下一代 CAR T 细胞。已经报道了许多用于 CAR T 细胞的可溶性辅助因子，并且已经通过全身注射测试了它们的治疗效果和毒性；因此，利用分泌辅助因子的 CAR T 细胞可能接近临床应用。在这里，我们回顾了已报道的可改善 CAR T 细胞治疗效果和减轻不良反应的各种分泌辅助因子。此外，我们还讨论了用于优化其有益效果的不同辅助因子表达系统。总之，我们证明将 CAR T 细胞与分泌辅助因子相结合将产生下一代 CAR T 细胞疗法，可用于更广泛类型的癌症，并为更复杂的合成免疫疗法提供先进工具。
