{"title":"PD-L1抗体的共表达增强了嵌合抗原受体T细胞的抗肿瘤作用","authors":"Shruti Lal, Guan Wang, Zhoushi Chen, X. Xiang, Chengyu Liang, Xue F. Huang, Si-Yi Chen","doi":"10.35248/2684-1266.19.5.119","DOIUrl":null,"url":null,"abstract":"Chimeric antigen receptor T (CAR-T) cell therapy against solid tumors has shown limited success in clinical trials. Solid tumors with highly immunosuppressive tumor microenvironment limit the anti-tumor efficacy of CAR-T cell therapy. Herein we generated a novel vector that co-express human mesothelin (MSLN)-targeted CAR and secretory human anti-programmed death ligand 1 (PD-L1) antibodies. The anti-PD-L1 antibodies secreted from the transduced T cells were able to block the interaction of PD-1/PD-L1 to overcome PD-L1-mediated immune suppression. The CAR-T cells targeting mesothelin and secreting PD-L1 antibodies enhanced cytolytic activity against MSLN+PD-L1+ tumor cells and increased the production of cytokines IL-2, TNFα, and IFNγ. The CAR-T cells targeting MSLN and secreting PD-L1 antibodies had enhanced anti-tumor efficacy when compared with the MSLN-targeted CAR-T cells in xenograft mouse models of mesothelioma, pancreatic and ovarian cancers. The results of this study demonstrated that the co-expression of PD-L1 antibody enhances the anti-tumor efficacy of CAR-T cell therapy against solid tumors.","PeriodicalId":22619,"journal":{"name":"The Journal of Cancer Research","volume":"63 1","pages":"1-9"},"PeriodicalIF":0.0000,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Co-expression of PD-L1 Antibodies Enhances the Anti-Tumor Efficacy of Chimeric Antigen Receptor T Cells\",\"authors\":\"Shruti Lal, Guan Wang, Zhoushi Chen, X. Xiang, Chengyu Liang, Xue F. Huang, Si-Yi Chen\",\"doi\":\"10.35248/2684-1266.19.5.119\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Chimeric antigen receptor T (CAR-T) cell therapy against solid tumors has shown limited success in clinical trials. Solid tumors with highly immunosuppressive tumor microenvironment limit the anti-tumor efficacy of CAR-T cell therapy. Herein we generated a novel vector that co-express human mesothelin (MSLN)-targeted CAR and secretory human anti-programmed death ligand 1 (PD-L1) antibodies. The anti-PD-L1 antibodies secreted from the transduced T cells were able to block the interaction of PD-1/PD-L1 to overcome PD-L1-mediated immune suppression. The CAR-T cells targeting mesothelin and secreting PD-L1 antibodies enhanced cytolytic activity against MSLN+PD-L1+ tumor cells and increased the production of cytokines IL-2, TNFα, and IFNγ. The CAR-T cells targeting MSLN and secreting PD-L1 antibodies had enhanced anti-tumor efficacy when compared with the MSLN-targeted CAR-T cells in xenograft mouse models of mesothelioma, pancreatic and ovarian cancers. The results of this study demonstrated that the co-expression of PD-L1 antibody enhances the anti-tumor efficacy of CAR-T cell therapy against solid tumors.\",\"PeriodicalId\":22619,\"journal\":{\"name\":\"The Journal of Cancer Research\",\"volume\":\"63 1\",\"pages\":\"1-9\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Cancer Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.35248/2684-1266.19.5.119\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Cancer Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.35248/2684-1266.19.5.119","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Co-expression of PD-L1 Antibodies Enhances the Anti-Tumor Efficacy of Chimeric Antigen Receptor T Cells
Chimeric antigen receptor T (CAR-T) cell therapy against solid tumors has shown limited success in clinical trials. Solid tumors with highly immunosuppressive tumor microenvironment limit the anti-tumor efficacy of CAR-T cell therapy. Herein we generated a novel vector that co-express human mesothelin (MSLN)-targeted CAR and secretory human anti-programmed death ligand 1 (PD-L1) antibodies. The anti-PD-L1 antibodies secreted from the transduced T cells were able to block the interaction of PD-1/PD-L1 to overcome PD-L1-mediated immune suppression. The CAR-T cells targeting mesothelin and secreting PD-L1 antibodies enhanced cytolytic activity against MSLN+PD-L1+ tumor cells and increased the production of cytokines IL-2, TNFα, and IFNγ. The CAR-T cells targeting MSLN and secreting PD-L1 antibodies had enhanced anti-tumor efficacy when compared with the MSLN-targeted CAR-T cells in xenograft mouse models of mesothelioma, pancreatic and ovarian cancers. The results of this study demonstrated that the co-expression of PD-L1 antibody enhances the anti-tumor efficacy of CAR-T cell therapy against solid tumors.