肿瘤细胞治疗研究
英文原题：Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?
CAR-T 细胞被称为革命性的活体药物，在某些血液系统恶性肿瘤如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）中，凭借其成功的临床结局获得美国食品药品监督管理局（FDA）批准，从而扭转了传统癌症治疗的格局。
CAR-T 细胞被视为革命性的活体药物；凭借良好的临床结局，它们已获美国食品药品监督管理局（FDA）批准，用于治疗 B 急性淋巴细胞白血病（B-ALL）和弥漫大 B 细胞淋巴瘤（DLBCL）等某些血液系统恶性肿瘤，改变了传统癌症治疗格局。然而，由于肿瘤抗原表达异质性及免疫抑制性肿瘤微环境（TME）等限制，CAR-T 在实体瘤治疗中尚未取得成功；这些因素会妨碍 CAR-T 到达肿瘤部位、浸润、受到刺激、活化和持续存在。本文探讨多种策略，包括加强疫苗接种和设计配套方案，以支持 CAR-T 扩增、增殖和杀伤肿瘤的能力；同时着重介绍触发内源性抗肿瘤反应、克服 CAR-T 肿瘤组织浸润不足及缺乏明确肿瘤特异性抗原等局限的新策略。最后总结这些方法如何应对上述艰巨挑战。
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.
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