Immunostimulatory CKb11 gene combined with immune checkpoint PD-1/PD-L1 blockade activates immune response and simultaneously overcomes the immunosuppression of cancer  

作　　者：Wen Nie Yihong He Xue Mi Shi He Jing Chen Yunchu Zhang Bilan Wang Songping Zheng Zhiyong Qian Xiang Gao 

机构地区：[1]Department of Neurosurgery and Institute of Neurosurgery,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,West China Medical School,Sichuan University and Collaborative Innovation Center for Biotherapy,610041,Chengdu,PR China [2]Department of Pharmacy,West China Second University Hospital of Sichuan University,610041,Chengdu,PR China

出　　处：《Bioactive Materials》2024年第9期239-254,共16页生物活性材料（英文）

基　　金：supported by Sichuan Science and Technology Program(No.2023YFS0170,2023NSFSC1931);supported by Medical Science and Technology Project of Sichuan Provincial Health Commission(No.21PJ009);supported by the National Natural Science Foundation of China(No.32222046,32371545,82103635);supported by the Technological innovation research and development project of Chengdu Science and Technology Bureau(2022-YF05-01589-SN);The 1⋅3⋅5 project of excellent development of discipline of West China Hospital of Sichuan University(No.ZYGC21022).

摘　　要：Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells,resulting in high CKb11 secretion from tumor cells,successfully activating immune cells and increasing cytokine secretion to reshape the TME,and ultimately delaying tumor progression.The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME.It can cause high expression of IFN-γ,which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells.Therefore,combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor outcome.Thus,utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites,thereby reshaping immunosuppressive TME for cancer treatment,has great potential as an immunogene therapy in clinical applications.

关 键 词：Ovarian cancer Immunogene therapy CKb11 Immune checkpoint PD-1/PD-L1 NANOMEDICINE 

分 类 号：R730.51[医药卫生—肿瘤]