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Immunostimulatory ckb11 gene combined with immune checkpoint PD-1/PD-L1 blockade activates immune response and simultaneously overcomes the immunosuppression of cancer

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Bioactive Materials 2024年第9期39卷 239-254页

作者： Wen Nie Yihong He Xue Mi Shi He Jing Chen Yunchu Zhang Bilan Wang Songping Zheng Zhiyong Qian Xiang Gao Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for Biotherapy610041ChengduPR China Department of Pharmacy West China Second University Hospital of Sichuan University610041ChengduPR China

Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of *** 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 *** chemokine ckb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in *** 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 ***,combining ckb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor ***,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

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Non-viral vector mediated ckb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer

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Bioactive Materials 2021年第11期6卷 3678-3691页

作者： Wen Nie Ting Yu Xiaoxiao Liu Bilan Wang Tingting Li Yin Wu Xikun Zhou Lu Ma Yunfeng Lin Zhiyong Qian Xiang Gao Department of Neurosurgery1nd Institute of Neurosurgery State Key Laboratory of Biotherapy1nd Cancer CenterWest China HospitalWest China Medical SchoolSichuan University1nd Collaborative Innovation Center for BiotherapyChengdu610041PR China Department of Medical Oncology The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310003China Department of Pathology1nd Laboratory of Pathology State Key Laboratory of BiotherapyWest China HospitalWest China School of MedicineSichuan UniversityChina Department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration1nd Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical UniversityXuzhou221000China Department of Pharmacy West China Second University Hospital of Sichuan UniversityChengdu610041China State Key Laboratory of Oral Diseases National Clinical Research Centre for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China College of Biomedical Engineering Sichuan UniversityChengdu610041China

The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to *** and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the *** this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine *** delivery of plasmid ckb11(pckb11)by F-PPPD nanoparticles resulted in the high secretion of ckb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor *** of F-PPPD/pckb11 also significantly suppressed the cancer *** study demonstrated a nanotechnology-enabled delivery of pckb11,that remodeled the immunosuppressive TME,for cancer treatment.

关键词： Cancer Immunogene therapy ckb11 Nanocomposites Macrophages polarization

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