CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-macrophage versus CAR-T for solid tumors: The race between a rising star and a superstar.
CAR-macrophage versus CAR-T for solid tumors: The race between a rising star and a superstar.
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过继细胞治疗(ACT)因具有体内主动抗肿瘤能力,已成为最有前景的癌症免疫治疗策略之一。例如,工程化改造T细胞使其过表达嵌合抗原受体(CAR),已在部分血液系统恶性肿瘤治疗中显示强效疗效。然而,实体瘤CAR-T 疗效仍有限,原因包括实体瘤免疫抑制性肿瘤微环境(TME)、难以浸润肿瘤、缺乏肿瘤特异性抗原、抗原逃逸及严重副作用。相比之下,表达CAR的巨噬细胞(CAR-M)已成为另一种有前景的免疫治疗候选,特别适用于实体瘤。目前CAR-M仍处于起步阶段,仅有一项临床试验在推进,但其治疗实体瘤时相较CAR-T 展现潜在优势,包括抗肿瘤机制更丰富和肿瘤浸润能力更强。本文比较CAR-T 与CAR-M的CAR结构、抗肿瘤机制、治疗实体瘤面临的挑战,并总结实体瘤临床试验和实践所得启示,重点阐述CAR-M相较CAR-T 治疗实体瘤的潜在优势。理解二者的联系和差异,可为优化这两种实体瘤疗法提供新思路。
Adoptive cell therapy (ACT) has been demonstrated to be one of the most promising cancer immunotherapy strategies due to its active antitumor capabilities in vivo. Engineering T cells to overexpress chimeric antigen receptors (CARs), for example, has shown potent efficacy in the therapy of some hematologic malignancies.
However, the efficacy of chimeric antigen receptor T cell (CAR-T) therapy against solid tumors is still limited due to the immunosuppressive tumor microenvironment (TME) of solid tumors, difficulty in infiltrating tumor sites, lack of tumor-specific antigens, antigen escape, and severe side effects. In contrast, macrophages expressing CARs (CAR-macrophages) have emerged as another promising candidate in immunotherapy, particularly for solid tumors.
Now at its nascent stage (with only one clinical trial progressing), CAR-macrophage still shows inspiring potential advantages over CAR-T in treating solid tumors, including more abundant antitumor mechanisms and better infiltration into tumors. In this review, we discuss the relationships and differences between CAR-T and CAR-macrophage therapies in terms of their CAR structures, antitumor mechanisms, challenges faced in treating solid tumors, and insights gleaned from clinical trials and practice for solid tumors.
We especially highlight the potential advantages of CAR-macrophage therapy over CAR-T for solid tumors. Understanding these relationships and differences provides new insight into possible optimization strategies of both these two therapies in solid tumor treatment.
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