Dai Xiaofeng, Li Jitian, Chen Yiming, Ostrikov Kostya Ken
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
CAPsoul Biotechnology Company, Ltd, Beijing, China.
Front Oncol. 2022 Feb 23;12:837995. doi: 10.3389/fonc.2022.837995. eCollection 2022.
T cells engineered with chimeric antigen receptors (CAR) have demonstrated its widespread efficacy as a targeted immunotherapeutic modality. Yet, concerns on its specificity, efficacy and generalization prevented it from being established into a first-line approach against cancers. By reviewing challenges limiting its clinical application, ongoing efforts trying to resolve them, and opportunities that emerging oncotherapeutic modalities may bring to temper these challenges, we conclude that careful CAR design should be done to avoid the off-tumor effect, enhance the efficacy of solid tumor treatment, improve product comparability, and resolve problems such as differential efficacies of co-stimulatory molecules, cytokine storm, tumor lysis syndrome, myelosuppression and severe hepatotoxicity. As a promising solution, we propose potential synergies between CAR-T therapies and cold atmospheric plasma, an emerging onco-therapeutic strategy relying on reactive species, towards improved therapeutic efficacies and enhanced safety that deserve extensive investigations.
嵌合抗原受体（CAR）工程化的T细胞已证明其作为一种靶向免疫治疗方式具有广泛的疗效。然而，对其特异性、疗效和通用性的担忧使其无法成为对抗癌症的一线方法。通过回顾限制其临床应用的挑战、为解决这些挑战而正在进行的努力，以及新兴肿瘤治疗方式可能带来的缓和这些挑战的机遇，我们得出结论，应谨慎设计CAR以避免肿瘤外效应，提高实体瘤治疗的疗效，改善产品可比性，并解决共刺激分子的不同疗效、细胞因子风暴、肿瘤溶解综合征、骨髓抑制和严重肝毒性等问题。作为一个有前景的解决方案，我们提出CAR-T疗法与冷大气等离子体（一种依赖活性物质的新兴肿瘤治疗策略）之间可能存在协同作用，以提高治疗效果和增强安全性，这值得广泛研究。
