Unidad de Excelencia Instituto de Biología y Genética Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain.
Int J Mol Sci. 2021 Oct 29;22(21):11781. doi: 10.3390/ijms222111781.
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.
结直肠癌（CRC）是一个全球性的公共卫生问题，因为它是全球第三大常见癌症，也是第二大最致命的癌症。目前正在进行重大努力，以了解其分子途径，以及定义肿瘤相关抗原（TAA）和肿瘤特异性抗原（TSA）或新抗原，以便开发有效的治疗方法。细胞疗法目前越来越受到重视，特别是嵌合抗原受体（CAR）-T 细胞疗法，其中经过基因修饰的 T 细胞被重新定向针对感兴趣的肿瘤抗原。这种免疫疗法已成为癌症治疗中最有前途的进展之一，在血液恶性肿瘤中已成功证明其疗效。然而，在实体瘤中，如结肠癌，由于 TSA 短缺、靶标外肿瘤效应、CAR-T 细胞浸润低和免疫抑制微环境，难以取得相同的结果。为了解决 CRC 中的这些挑战，提出了新的方法，包括联合疗法、CAR-T 细胞的区域性给药和更复杂的 CAR 结构等。本文全面总结了 CRC 中 CAR-T 细胞疗法的现状，从潜在的肿瘤靶标到临床前研究和临床试验，以及这种新型抗肿瘤策略的局限性和未来展望。
