靶点重定向通用型TRUE-CAR-T治疗三阴性乳腺癌新模式的建立及评价

三阴性乳腺癌具有转移能力高、耐药性强和易复发等特点而成为乳腺癌治疗中一大难点。CAR-T是三阴性乳腺癌治疗的新方向，但方法面临着应用范围窄和有效性低的难题，而靶点问题是一个重要原因。本课题基于申请人前期国科金项目研究基础，首次从肿瘤自身靶点非依赖型CAR-T新思路出发，提出靶点重定向通用型CAR-T（TRUE-CAR-T）的设想，并从膜融合脂质体修饰肿瘤细胞膜靶点、TRUE-CAR-T策略疗效评估及其分子机制三个方面进行研究。本项目为拓宽CAR-T治疗三阴性乳腺癌应用并提高其疗效提供了新思路，也为我国潜在自主知识产权的TRUE-CAR-T治疗新模式的开发及向临床过渡提供了科学依据。

With the characteristics of high metastasis, strong drug resistance and easy recurrence, triple negative breast cancer has encountered a major treatment difficulty. CAR-T is a new direction in the treatment of triple negative breast cancer; however, the method faces the problem of narrow application range and low effectiveness, and one important cause is the target problem. Based on previous national science foundations, this project first proposed the idea of target-redirected universal CAR-T (TRUE-CAR-T) from the viewpoint of tumor-target independent CAR-T. Three aspects were studied: target modification of tumor cells using membrane fusion liposome, evaluation of therapeutic effect of TRUE-CAR-T strategy and its molecular mechanism. This project provides new ideas for broadening the application of CAR-T in the treatment of triple-negative breast cancer and improving its efficacy. It also provides a scientific basis for the development of a new TRUE-CAR-T treatment model with potential independent intellectual property rights in China.