Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of certain hematologic malignancies, yet its success in solid tumors has been limited by antigen heterogeneity, an immunosuppressive tumor microenvironment, and barriers to cell trafficking and persistence. To expand the reach of cellular immunotherapy, multiple immune cell types—γδ T cells, invariant NKT cells, virus-specific T cells, natural killer (ΝΚ) cells, and myeloid effectors such as macrophages and dendritic cells—are now being explored as alternative or complementary CAR platforms. Each lineage brings unique advantages, such as the innate cytotoxicity and safety profile of CAR NK cells, the tissue infiltration and microenvironment-modulating capacity of CAR macrophages, or the MHC-independent recognition offered by γδ T cells. Recent advances in pharmacological strategies, synthetic biology, and artificial intelligence provide additional opportunities to overcome barriers and optimize CAR design and manufacturing scale-up. Here, we review the state of the art in engineering diverse immune cells for solid tumor therapy, highlight safety considerations across autologous, allogeneic, and in vivo CAR cell therapy approaches, and provide our perspective on which platforms might best address current unmet clinical needs. Collectively, these developments lay the foundation for next-generation strategies to achieve durable immunotherapy responses in solid tumors.
嵌合抗原受体（CAR）T细胞疗法已彻底改变了某些血液系统恶性肿瘤的治疗格局，但其在实体瘤中的应用仍受限于抗原异质性、免疫抑制性肿瘤微环境以及细胞归巢与持久性障碍。为拓展细胞免疫疗法的适用范围，多种免疫细胞类型——γδ T细胞、恒定自然杀伤T细胞、病毒特异性T细胞、自然杀伤（NK）细胞以及巨噬细胞和树突状细胞等髓系效应细胞——正被探索作为替代性或补充性CAR平台。每种细胞谱系均具有独特优势：如CAR-NK细胞兼具天然细胞毒性与安全性特征，CAR-巨噬细胞具有组织浸润与微环境调节能力，γδ T细胞则能实现不依赖MHC的抗原识别。药理学策略、合成生物学与人工智能领域的最新进展为突破现有障碍、优化CAR设计与规模化生产提供了新机遇。本文系统综述了用于实体瘤治疗的多类工程化免疫细胞研究进展，重点探讨了自体、异体及体内CAR细胞疗法中的安全性考量，并对不同平台解决当前未满足临床需求的潜力提出展望。这些进展共同为在实体瘤中实现持久免疫治疗应答的下一代策略奠定了坚实基础。
Expanding Immunotherapy Beyond CAR T Cells: Engineering Diverse Immune Cells to Target Solid Tumors
肿瘤(癌症)患者之家