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
克服实体瘤屏障：装甲 CAR-T 细胞治疗
英文原题：Overcoming solid-tumor barriers: armored CAR-T cell therapy.
查看英文原题
Overcoming solid-tumor barriers: armored CAR-T cell therapy.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法在血液系统恶性肿瘤中显示出显著临床获益，但由于多种障碍，在实体瘤中的疗效仍较低，包括肿瘤浸润有限、免疫抑制性微环境，以及肿瘤抗原表达异质或特异性不足。通过工程化改造CAR-T 细胞，使其表达趋化因子受体、降解细胞外基质成分的酶、促炎细胞因子或调节免疫抑制信号的因子，可赋予CAR-T 细胞克服实体瘤相关障碍的能力。然而，将有前景的临床前结果转化为实体瘤患者可靠的临床获益仍具挑战。本综述批判性考察新兴CAR-T 细胞装甲化策略，指出关键转化障碍，并强调需要创新的人体相关疾病模型、安全性设计和治疗策略，推动有效临床转化。
展开英文摘要原文
Chimeric antigen receptor (CAR)-T cell therapy has shown significant clinical benefit in hematologic malignancies but remains less effective in solid tumors due to multiple barriers, including limited tumor infiltration, immunosuppressive microenvironments, and heterogeneity or imperfect specificity in tumor-antigen expression.
'Armoring' CAR-T cells to express chemokine receptors, enzymes that degrade extracellular matrix components, proinflammatory cytokines, or factors that modulate immunosuppressive signals could empower CAR-T cells to overcome barriers associated with solid tumors.
However, translating promising preclinical results into reliable clinical benefit for patients with solid tumors remains challenging. This review critically examines emerging CAR-T cell armoring approaches and highlights key translational hurdles and the need for innovations in human-relevant disease models, safety designs, and treatment strategies for effective translation.
论文信息
- 作者
- Kwon N、Chen YY
- 第一作者单位
- Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.United States
- 通讯作者单位
- Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Parker Institute for Cancer Immunotherapy Center at UCLA, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Electronic address: yvchen@ucla.edu.United States
- 文献类型
- 综述
- 期刊
- Trends in cancer2025 Oct
- 原文标识
- PubMed 40940282 · DOI 10.1016/j.trecan.2025.08.009