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:Targeting Macrophages in Immunotherapy: The Ascent of CAR-Macrophages.
Targeting Macrophages in Immunotherapy: The Ascent of CAR-Macrophages.
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嵌合抗原受体(CAR)工程化免疫细胞疗法革新了癌症治疗,CAR-T 细胞对血液系统恶性肿瘤具有显著疗效。然而,CAR-T 及其他淋巴细胞疗法治疗实体瘤仍受限,主要原因是免疫抑制性肿瘤微环境及效应细胞浸润不足。近年来,CAR巨噬细胞(CAR-M)免疫疗法成为克服这些障碍的有前景策略。利用巨噬细胞内在的肿瘤趋向性、吞噬功能和抗原呈递能力,CAR-M在靶向实体瘤方面具有独特优势。本综述全面介绍CAR巨噬细胞免疫疗法的发展及现状,包括CAR设计和巨噬细胞工程的进展、临床前和临床研究进度,以及抗肿瘤活性的机制认识。文章批判性评估CAR-M方法的优势和局限,讨论细胞来源、持久性和安全性等持续挑战,并探讨提高治疗效力的创新策略。最后展望CAR巨噬细胞疗法的未来及其潜在临床影响,强调其在不断演进的癌症免疫治疗中的新兴作用。
Chimeric antigen receptor (CAR)-engineered immune cell therapies have revolutionized cancer treatment, with CAR-T cells demonstrating remarkable efficacy against hematological malignancies.
However, the effectiveness of CAR-T and other lymphocyte-based therapies against solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment and poor infiltration of effector cells. Recently, CAR-macrophage (CAR-M) immunotherapy has emerged as a promising strategy to overcome these barriers. Leveraging the innate tumor-homing ability, phagocytic function, and antigen-presenting capacity of macrophages, CAR-M therapies offer unique advantages for targeting solid tumors.
This review provides a comprehensive overview of the development and current state of CAR-Macrophage immunotherapy, including advances in CAR design and macrophage engineering, preclinical and clinical progress, and mechanistic insights into their anti-tumor activity. The review critically examined both the benefits and limitations of CAR-M approaches, addressing persistent challenges such as cell sourcing, durability, and safety, while also exploring innovative strategies to enhance therapeutic efficacy.
Finally, future perspectives and the potential clinical impact of CAR-macrophage therapies were outlined, underscoring their emerging role in the evolving landscape of cancer immunotherapy.
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