Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, Iran.
Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Front Immunol. 2022 May 11;13:795164. doi: 10.3389/fimmu.2022.795164. eCollection 2022.
Chimeric antigen receptor T-cells (CAR-Ts) are known as revolutionary living drugs that have turned the tables of conventional cancer treatments in certain hematologic malignancies such as B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) by achieving US Food and Drug Administration (FDA) approval based on their successful clinical outcomes. However, this type of therapy has not seen the light of victory in the fight against solid tumors because of various restricting caveats including heterogeneous tumor antigen expression and the immunosuppressive tumor microenvironments (TME) that negatively affect the tumor-site accessibility, infiltration, stimulation, activation, and persistence of CAR-Ts. In this review, we explore strategic twists including boosting vaccines and designing implementations that can support CAR-T expansion, proliferation, and tumoricidal capacity. We also step further by underscoring novel strategies for triggering endogenous antitumor responses and overcoming the limitation of poor CAR-T tumor-tissue infiltration and the lack of definitive tumor-specific antigens. Ultimately, we highlight how these approaches can address the mentioned arduous hurdles.
嵌合抗原受体 T 细胞（CAR-T 细胞）被誉为革命性的活体药物，在某些血液系统恶性肿瘤中，如 B 细胞急性淋巴细胞白血病（B-ALL）和弥漫性大 B 细胞淋巴瘤（DLBCL），通过基于成功临床结果获得美国食品和药物管理局（FDA）批准，颠覆了传统癌症治疗方法。然而，由于各种限制因素，包括肿瘤抗原表达异质性和抑制性肿瘤微环境（TME），这些因素会影响 CAR-T 细胞在肿瘤部位的可及性、浸润、刺激、激活和持久性，这种治疗方法在针对实体瘤的治疗中尚未取得胜利。在这篇综述中，我们探讨了一些策略性的改进，包括增强疫苗和设计实施方法，以支持 CAR-T 的扩增、增殖和杀瘤能力。我们还进一步强调了触发内源性抗肿瘤反应和克服 CAR-T 细胞在肿瘤组织中浸润不良以及缺乏明确的肿瘤特异性抗原的局限性的新策略。最终，我们强调了这些方法如何解决上述困难。
