工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cutting-Edge CAR Engineering: Beyond T Cells.
Cutting-Edge CAR Engineering: Beyond T Cells.
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嵌合抗原受体(CAR)-T过继性细胞疗法是治疗癌症最有前景的先进疗法之一,在血液系统恶性肿瘤中取得了前所未有的疗效。然而,其在实体瘤中仍缺乏疗效,可能是因为工程化T细胞在免疫抑制性肿瘤微环境(TME)中变得失活。在TME中,髓系(M)细胞是肿瘤浸润率最高的免疫抑制性细胞类型之一。这些细胞与其他免疫细胞相互作用,介导免疫抑制并促进血管生成。近年来,CAR-M细胞疗法的发展被提出作为一种新的候选免疫疗法,具有良好的疗效潜力。这种替代性CAR策略可能提高CAR治疗在实体瘤中的疗效、生存期、持久性和安全性。这仍然是癌症研究中的一个关键前沿领域,并为下一代个性化医疗克服TME耐药开辟了新的可能性。然而,CAR-M的确切作用机制及其对TME的影响仍知之甚少。在此,我们总结了CAR-固有免疫细胞和CAR-M细胞免疫疗法的基础、转化和临床研究结果,从其工程化和机制研究到临床前和临床开发。
Chimeric antigen receptor (CAR)-T adoptive cell therapy is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in haematological malignancies.
However, it still lacks efficacy in solid tumours, possibly because engineered T cells become inactive within the immunosuppressive tumour microenvironment (TME). In the TME, cells of the myeloid lineage (M) are among the immunosuppressive cell types with the highest tumour infiltration rate. These cells interact with other immune cells, mediating immunosuppression and promoting angiogenesis.
Recently, the development of CAR-M cell therapies has been put forward as a new candidate immunotherapy with good efficacy potential. This alternative CAR strategy may increase the efficacy, survival, persistence, and safety of CAR treatments in solid tumours. This remains a critical frontier in cancer research and opens up a new possibility for next-generation personalised medicine to overcome TME resistance.
However, the exact mechanisms of action of CAR-M and their effect on the TME remain poorly understood.
Here, we summarise the basic, translational, and clinical results of CAR-innate immune cells and CAR-M cell immunotherapies, from their engineering and mechanistic studies to preclinical and clinical development.
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