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-armored-cell therapy in solid tumor treatment.
CAR-armored-cell therapy in solid tumor treatment.
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过去十年,嵌合抗原受体(CAR)T细胞疗法成为一种突破性抗癌免疫治疗方式。该疗法通过基因工程在T细胞表面构建CAR。CAR由抗体或配体来源结构域与T细胞受体(TCR)结构域组合而成,使T细胞能够特异性结合肿瘤细胞并被激活。然而,CAR-T 细胞治疗实体瘤的疗效仍未确定,原因包括肿瘤归巢和浸润能力不足,以及免疫抑制性肿瘤微环境(TME)等挑战。针对这些问题,研究者已开发CARNK 细胞(CAR-NK)和CAR巨噬细胞(CAR-M)作为实体瘤补充策略。CAR-NK细胞不需要HLA相容性,毒性较低,因此被视为CAR-T 细胞的潜在替代选择。此外,CAR-M免疫疗法也在研究中,已显示吞噬和呈递肿瘤抗原的能力。本研究讨论CAR-T、CAR-NK及CAR-M细胞治疗实体瘤的特点、优势和局限,并提出提高CAR宿主细胞免疫疗法效力的潜在解决方案。
Over the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a revolutionary immunotherapeutic approach to combat cancer. This therapy constructs a CAR on the surface of T cells through genetic engineering techniques. The CAR is formed from a combination of antibody-derived or ligand-derived domains and T-cell receptor (TCR) domains. This enables T cells to specifically bind to and activate against tumor cells.
However, the efficacy of CAR-T cells in solid tumors remains inconclusive due to several challenges such as poor tumor trafficking, infiltration, and the immunosuppressive tumor microenvironment (TME). In response, CAR natural killer (CAR-NK) and CAR macrophages (CAR-M) have been developed as complementary strategies for solid tumors. CAR-NK cells do not require HLA compatibility, demonstrate reduced toxicity, and are thus seen as potential substitutes for CAR-T cells.
Furthermore, CAR-M immunotherapy is also being researched and has shown phagocytic capabilities and tumor-antigen presentation.
This study discusses the features, advantages, and limitations of CAR-T, CAR-NK, and CAR-M cells in the treatment of solid tumors and suggests prospective solutions for enhancing the efficacy of CAR host-cell-based immunotherapy.
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