嵌合抗原受体巨噬细胞免疫疗法及其在实体瘤治疗中的应用

CAR-M Cell-based Immunotherapy Directed Against Solid Tumors

嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)疗法在血液肿瘤中取得了显著成功,但在实体瘤的治疗中收效甚微。相比之下,固有免疫细胞在癌症中的临床应用还没有得到广泛开发。巨噬细胞是肿瘤微环境中主要的固有免疫细胞并具有较强的吞噬和浸润能力,最近研究发现嵌合抗原受体巨噬细胞(chimeric antigen receptor macrophage,CAR-M)免疫疗法在多种实体瘤中发挥重要的抗肿瘤效应。本文总结了近年来CAR-M治疗肿瘤的相关研究,旨在探究其对实体瘤的潜在治疗价值,为其未来的临床应用提供参考。

Chimeric antigen receptor T cells(CAR-T)have achieved remarkable success in the treatment of hematological cancers,but little progress in solid tumors.Meanwhile,innate immune cells-based tumor immunotherapy has been scarcely developed.Macrophages detect and clear malignant cells through phagocytosis and innate immune sensing,thus being potential targets for cancer immunotherapy.Promising evidence from preclinical studies have shown chimeric antigen receptor macrophages(CAR-M)as an effective therapeutic strategy in solid tumors.This review sketches the prospect of CAR-immune cell therapeutics and emphasizes current status and perspective of CAR-M cell therapy trials and limitations associated with CAR-M.We also describe CAR-M can be manufactured from pre-existing cell lines or induced pluripotent stem cells,while transfection vectors for CAR-M show different characteristics,highlighting CAR-M as a next-generation therapeutic modality linking the closely intertwined innate and adaptive immunity to induce efficacious antitumor immune responses.