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:Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells.
Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells.
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结直肠癌(CRC)是全球公共卫生问题,按全球发病率和致死率分别位居第三和第二。当前正在大力研究其分子通路,并确定肿瘤相关抗原(TAA)、肿瘤特异性抗原(TSA)或新抗原,以开发有效治疗方法。细胞疗法日益受到重视,尤其是嵌合抗原受体(CAR)T细胞疗法,该疗法通过基因修饰使T细胞重新定向至目标肿瘤抗原。CAR-T 免疫疗法已成为癌症治疗最有前景的进展之一,并在血液系统恶性肿瘤中成功显示疗效。然而,在结肠癌等实体瘤中,由于TSA不足、靶向肿瘤外组织效应、CAR-T 细胞浸润较低和免疫抑制性微环境等因素,难以获得同样的结果。为应对CRC中的这些挑战,研究者提出多种新方法,包括联合治疗、局部给予CAR-T 细胞以及更复杂的CAR结构等。本文全面总结CRC CAR-T 细胞治疗现状,涵盖潜在肿瘤靶点、临床前研究和临床试验,以及这一新型抗肿瘤策略的局限和未来展望。
Colorectal cancer (CRC) is a global public health problem as it is the third most prevalent and the second most lethal cancer worldwide. Major efforts are underway to understand its molecular pathways as well as to define the tumour-associated antigens (TAAs) and tumour-specific antigens (TSAs) or neoantigens, in order to develop an effective treatment.
Cell therapies are currently gaining importance, and more specifically chimeric antigen receptor (CAR)-T cell therapy, in which genetically modified T cells are redirected against the tumour antigen of interest. This immunotherapy has emerged as one of the most promising advances in cancer treatment, having successfully demonstrated its efficacy in haematological malignancies.
However, in solid tumours, such as colon cancer, it is proving difficult to achieve the same results due to the shortage of TSAs, on-target off-tumour effects, low CAR-T cell infiltration and the immunosuppressive microenvironment. To address these challenges in CRC, new approaches are proposed, including combined therapies, the regional administration of CAR-T cells and more complex CAR structures, among others.
This review comprehensively summarises the current landscape of CAR-T cell therapy in CRC from the potential tumour targets to the preclinical studies and clinical trials, as well as the limitations and future perspectives of this novel antitumour strategy.
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