肿瘤细胞治疗研究
英文原题：Bioengineering CAR-T cells to function in hostile tumor microenvironments.
Bioengineering CAR-T cells to function in hostile tumor microenvironments.
嵌合抗原受体（CAR）-T 细胞疗法在血液系统恶性肿瘤中取得了显著成功，但在实体瘤中仍基本无效。
嵌合抗原受体（CAR）T 细胞疗法在血液系统恶性肿瘤中取得显著成功，但对实体瘤仍基本无效。越来越多证据表明，这一局限不仅源于抗原识别不理想，也因为治疗细胞无法到达并在抑制性肿瘤微环境中发挥功能。本综述总结 CAR-T 细胞生物工程近期进展，重点介绍旨在克服实体瘤物理屏障、免疫抑制信号、代谢应激和细胞耗竭的策略。实体瘤是全球癌症相关死亡的主要原因之一。文章重点阐述已在体内验证、可增强肿瘤迁移、瘤内滞留、应激抵抗和抗免疫抑制能力的策略，并说明临床转化所需解决的关键挑战和安全性考量。
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in hematological malignancies but remains largely ineffective in solid tumors. Accumulating evidence indicates that this limitation reflects not only suboptimal antigen recognition but also the inability of therapeutic cells to reach and function within the suppressive tumor microenvironment. This review synthesizes recent advances in CAR-T cell bioengineering aimed at overcoming physical barriers, immunosuppressive signaling, metabolic stress, and cellular exhaustion that characterize solid tumors, which are a leading cause of cancer-related mortality worldwide. We highlight in vivo-validated strategies that enhance tumor trafficking, intratumoral retention, stress resilience, and resistance to immunosuppression, while delineating key translational challenges and safety considerations required for clinical translation.
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