肿瘤细胞治疗研究
英文原题：Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.
全球癌症负担日益加重，亟需创新的治疗策略。
全球癌症负担不断增加，亟需创新治疗策略。细胞疗法是肿瘤学领域的一项重大突破，已从CAR-T（CAR-T）细胞成功用于血液系统恶性肿瘤，迅速发展为多平台格局，多种策略同步推进。目前研究聚焦于T细胞受体工程化T（TCR-T）细胞、TIL（肿瘤浸润淋巴细胞）、γδ T细胞、CAR-NK细胞、CAR巨噬细胞（CAR-M），以及基于树突状细胞（DC）、B细胞和干细胞的多种策略。转化研究范式正从相对成熟的血液系统恶性肿瘤领域，扩展到患病更普遍且机制更复杂的实体瘤领域。近年来，该领域显现出从自体疗法向异基因“现货型”平台拓展的明确趋势。CAR-NK和CAR-NKT细胞疗法等方法因免疫原性较低、移植物抗宿主病（GvHD）风险较小，显示出显著临床潜力。同时，可直接在体内原位递送CAR基因的体内工程技术也正在兴起，有望通过绕过复杂的体外操作降低成本并简化制造流程。本综述系统概述这些策略的最新进展，重点介绍其作用机制、靶抗原和临床转化。尽管已取得进展，仍面临肿瘤异质性、免疫抑制性肿瘤微环境（TME）和治疗相关毒性等重大挑战。未来研究将聚焦新靶点发现、毒性管理改善和可扩展制造工艺。多组学分析、人工智能和合成生物学等多学科技术的整合，将推动细胞疗法实现更安全、更有效且更广泛可及的应用。
The increasing global burden of cancer necessitates innovative therapeutic strategies. Cell therapy represents a major breakthrough in oncology, evolving rapidly from the successful application of chimeric antigen receptor T (CAR-T) cells in hematologic malignancies to a multiplatform landscape characterized by the concurrent development of diverse strategies. Current research focuses on T cell receptor-engineered T (TCR-T) cells, tumor-infiltrating lymphocytes (TILs), gamma delta ( ) T cells, CAR-natural killer (CAR-NK) cells, CAR-macrophages (CAR-Ms), and various strategies based on dendritic cells (DCs), B cells, and stem cells. The translational paradigm is expanding from the relatively mature field of hematologic malignancies to the more prevalent and mechanistically complex domain of solid tumors. In recent years, this field has exhibited a clear trend toward expansion from autologous therapies to allogeneic "off-the-shelf" platforms. Approaches such as CAR-NK and CAR-natural killer T (CAR-NKT) cell therapies exhibit significant clinical potential because of their low immunogenicity and reduced risk of graft-versus-host disease (GvHD). Concurrently, in vivo engineering technologies that directly deliver CAR genes in situ are emerging as promising approaches to lower costs and simplify manufacturing by bypassing complex ex vivo procedures. This review systematically outlines recent advances in these strategies, focusing on their mechanisms of action, target antigens, and clinical translation. Despite progress, formidable challenges remain, including tumor heterogeneity, the immunosuppressive tumor microenvironment (TME), and therapy-related toxicity. To address these challenges, future research will focus on novel target discovery, enhanced toxicity management, and scalable manufacturing processes. The integration of multidisciplinary technologies, such as multiomics analysis, artificial intelligence, and synthetic biology, will advance cell therapies toward safer, more effective, and widely accessible applications.
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