基于肝脏移植的同种异体T-rapa抗肿瘤免疫治疗体系的实验研究

肝脏是一种免疫器官，具有移植物抗肿瘤效应(GVT), 本课题利用肝移植这一重要免疫学特征，①通过对供肝的免疫预处理，强化移植肝脏的GVT作用；②运用供肝同源的Rapamycin抵抗的T细胞进行过继免疫治疗；③通过肿瘤抗原GUCY2C免疫T-rapa细胞，增强其特异性与记忆性。 由此，Rapamycin可保障移植肝的存活与耐受，但不影响T-rapa细胞的抗肿瘤作用，同时移植肝的免疫特惠作用可保护T-rapa细胞，并为其提供免疫生发的NICHE，从而形成相互整合的免疫治疗体系，达到强烈、持续的抗肿瘤效果。

Liver is an immune organ with graft-versus-tumor effects (GVT). Our project would utilize this important immunological feature, ① to enhance the GVT effects by immune activation of liver grafts,② to apply the immunotherapy with rapamycin resistant T cells of donor origin,③ to enhance the immune specificity and memory of T-rapa by immunization with tumor specific antigen-GUCY2C. Thus, rapamycin could protect the liver graft from rejection without affect the anti- tumor effect of T-rapa. Meanwhile, the immune privilege effect of graft liver could protect T-rapa, and provide a Niche for their immune development as well. By this project, an integrated immunotherapy based on liver transplants is supposed to display intense and persistent anti-tumor effects.