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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Recent Advances in CAR-Based Solid Tumor Immunotherapy.
Recent Advances in CAR-Based Solid Tumor Immunotherapy.
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使用嵌合抗原受体(CAR)技术的过继细胞疗法是癌症免疫治疗中最先进的工程平台之一。CAR-T 细胞在血液系统恶性肿瘤的治疗中已显示出显著疗效。
然而,其在实体瘤中的局限性包括免疫抑制性肿瘤微环境(TME)、肿瘤浸润不足、毒性以及缺乏肿瘤特异性抗原。尽管近期CAR-T 细胞设计的进展——如共刺激结构域的引入和装甲CAR-T 细胞的开发——在治疗实体瘤方面显示出有前景的结果,但仍存在需要解决的挑战。为克服这些局限性,其他免疫细胞,如自然杀伤(NK)细胞和巨噬细胞(M),已被开发为实体瘤高效癌症免疫治疗的有吸引力的选择。CAR-NK细胞表现出显著的临床改善,具有“现货型”可用性和低毒性。CAR-M细胞具有有前景的治疗潜力,因为巨噬细胞能够浸润实体瘤的TME。
在此,我们综述了与用于实体瘤的工程化免疫细胞癌症免疫治疗相关的最新进展和未来展望。我们还总结了正在进行的临床研究,这些研究探讨了工程化免疫细胞(如CAR-T、CAR-NK和CAR-M)靶向实体瘤的安全性和有效性。
Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies.
However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in treating solid tumors, there are still challenges that need to be addressed.
To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors.
Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors.
We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors.
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