Department of Internal Medicine and Gastroenterology, Mazovian "Bródnowski" Hospital, 03-242 Warsaw, Poland.
Laboratory of Cellular and Genetic Therapies, Medical University of Warsaw, 02-091 Warsaw, Poland.
Cells. 2024 Jan 4;13(1):101. doi: 10.3390/cells13010101.
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of malignant and non-malignant disorders. CARs are synthetic transmembrane receptors expressed on genetically modified immune effector cells, including T cells, natural killer (NK) cells, or macrophages, which are able to recognize specific surface antigens on target cells and eliminate them. CAR-modified immune cells mediate cytotoxic antitumor effects via numerous mechanisms, including the perforin and granzyme pathway, Fas and Fas Ligand (FasL) pathway, and cytokine secretion. High hopes are associated with the prospective use of the CAR-T strategy against solid cancers, especially the ones resistant to standard oncological therapies, such as pancreatic cancer (PC). Herein, we summarize the current pre-clinical and clinical studies evaluating potential tumor-associated antigens (TAA), CAR-T cell toxicities, and their efficacy in PC.
嵌合抗原受体 (CAR) T 细胞疗法已经彻底改变了恶性和非恶性疾病的治疗方法。CAR 是表达在经过基因修饰的免疫效应细胞(包括 T 细胞、自然杀伤 (NK) 细胞或巨噬细胞)表面的合成跨膜受体,能够识别靶细胞表面的特定抗原并将其清除。CAR 修饰的免疫细胞通过多种机制介导细胞毒性抗肿瘤作用,包括穿孔素和颗粒酶途径、Fas 和 Fas 配体 (FasL) 途径以及细胞因子分泌。人们对 CAR-T 策略在实体瘤中的潜在应用寄予厚望,尤其是对标准肿瘤治疗方法耐药的实体瘤,如胰腺癌 (PC)。在此,我们总结了目前评估 PC 中潜在肿瘤相关抗原 (TAA)、CAR-T 细胞毒性及其疗效的临床前和临床研究。