Challenges and interventions of chimeric antigen receptor-T cell therapy in solid tumors.

Shasha Liu, Yi Zhang
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Abstract

Adoptive cellular therapy is rapidly improving immunotherapy in hematologic malignancies and several solid tumors. Remarkable clinical success has been achieved in chimeric antigen receptor (CAR)-T cell therapy which represents a paradigm-shifting strategy for the treatment of hematological malignancies. However, many challenges such as resistance, antigen heterogeneity, poor immune cell infiltration, immunosuppressive microenvironment, metabolic obstructive microenvironment, and T cell exhaustion remain as barriers to broader application especially in solid tumors. Encouragingly, the development of new approaches such as multidimensional omics and biomaterials technologies was aided to overcome these barriers. Here, in this perspective, we focus on the most recent clinical advancements, challenges, and strategies of immune cellular therapy in solid tumor treatment represented by CAR-T cell therapy, to provide new ideas to further overcome the bottleneck of immune cell therapy and anticipate future clinical advances.

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嵌合抗原受体- t细胞治疗实体瘤的挑战和干预措施。
过继细胞疗法正在迅速改善血液恶性肿瘤和几种实体瘤的免疫治疗。嵌合抗原受体(CAR)-T细胞治疗取得了显著的临床成功,它代表了血液系统恶性肿瘤治疗的范式转变策略。然而,许多挑战,如耐药性、抗原异质性、免疫细胞浸润不良、免疫抑制微环境、代谢阻塞性微环境和T细胞耗竭等,仍然是广泛应用的障碍,特别是在实体肿瘤中。令人鼓舞的是,多维组学和生物材料技术等新方法的发展有助于克服这些障碍。本文从这一角度出发,聚焦以CAR-T细胞治疗为代表的免疫细胞治疗在实体瘤治疗中的最新临床进展、挑战和策略,为进一步突破免疫细胞治疗的瓶颈提供新的思路,并对未来的临床进展进行预测。
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