Xu Tongpeng, Wang Chen, Wang Xiaoyan, Wang Enxiu, Wang Bo, Sun Ming
Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Nanjing CART Medical Technology Co., Ltd, Nanjing, 210032, People's Republic of China.
Med Oncol. 2023 Jul 5;40(8):226. doi: 10.1007/s12032-023-02084-9.
While CAR-T cell therapy has shown success against hematological tumors, its effectiveness for solid tumors, including ovarian cancer, remains unsatisfactory. This study aimed to develop and evaluate the efficacy of novel chimeric antigen receptor T (CAR-T) cells targeting PTK7 through TREM1/DAP12 signaling against ovarian cancer. The expression of PTK7 in ovarian cancer tissues and cells was evaluated using immunohistochemical staining and flow cytometric analysis. The anti-tumor effects of PTK7 CAR-T cells were assessed in vitro using real-time cell analysis and enzyme-linked immunosorbent assay, and in vivo using a xenograft tumor model. PTK7 was significantly expressed in ovarian cancer tissues and cells. PTK7-targeting CAR-T cells based on TREM1/DAP12 signaling exhibited potent cytotoxicity against ovarian cancer cells expressing PTK7 in vitro, and effectively eradicated tumors in vivo. Our findings suggest that TREM1/DAP12-based PTK7 CAR-T cells have potential as a treatment strategy for ovarian cancer. Further studies are needed to evaluate the safety and efficacy of this approach in clinical trials.
虽然嵌合抗原受体T细胞(CAR-T)疗法已在血液肿瘤治疗中取得成功,但其对包括卵巢癌在内的实体瘤的疗效仍不尽人意。本研究旨在开发并评估通过TREM1/DAP12信号靶向PTK7的新型嵌合抗原受体T(CAR-T)细胞对卵巢癌的疗效。采用免疫组织化学染色和流式细胞术分析评估PTK7在卵巢癌组织和细胞中的表达。使用实时细胞分析和酶联免疫吸附测定法在体外评估PTK7 CAR-T细胞的抗肿瘤作用,并使用异种移植肿瘤模型在体内进行评估。PTK7在卵巢癌组织和细胞中显著表达。基于TREM1/DAP12信号的靶向PTK7的CAR-T细胞在体外对表达PTK7的卵巢癌细胞表现出强大的细胞毒性,并在体内有效根除肿瘤。我们的研究结果表明,基于TREM1/DAP12的PTK7 CAR-T细胞有潜力作为卵巢癌的一种治疗策略。需要进一步研究来评估这种方法在临床试验中的安全性和疗效。