Nanovaccines are used as delivery platforms for antigens and adjuvants, which activate antigen-presenting cells (APCs) and enhance anticancer immune responses.1,2 Researchers have recently developed a self-assembled n...Nanovaccines are used as delivery platforms for antigens and adjuvants, which activate antigen-presenting cells (APCs) and enhance anticancer immune responses.1,2 Researchers have recently developed a self-assembled nanocomplex using a polysorbitol-co-PEI (PSPEI) polymer complexed with poly(I:C) (PIC). By binding to different surface proteins, this nanocomplex enhances the intracellular delivery of cargos and induces potent anticancer immune responses against melanoma cells.3 We have previously demonstrated that PD-1/PD-L1 blockade enhanced the efficacy of DC-based cancer immunotherapy.4,5 Moreover, the combination of nanomedicines and PD-L1 blockade has been reported to enhance CD8+ T cell activation and inhibit immunosuppressive cells within the tumor microenvironment.6 In the present study, we investigated the therapeutic efficacy of a combinatorial treatment comprising the immunoadjuvant nanocomplex PSPEI-PIC, a DC vaccine, and PD-L1 blockade in a murine colon cancer model.展开更多
The use of natural killer(NK)cells is a promising and safe immunotherapeutic approach in the field of cancer immunotherapy.However,combination treatments are required to enhance the effector functions and therapeutic ...The use of natural killer(NK)cells is a promising and safe immunotherapeutic approach in the field of cancer immunotherapy.However,combination treatments are required to enhance the effector functions and therapeutic efficacy of NK cells.In this study,we investigated the potential of daratumumab(Dara),bortezomib,and dexamethasone(Dvd)to augment the antitumor effects of NK cells in a multiple myeloma(MM)xenograft mouse model.NK cells were expanded and activated using the K562-OX40 ligand and membrane-bound IL-18 and IL-21 in the presence of IL-2 and IL-15 from peripheral blood mononuclear cells from MM patients.A human MM xenograft model was established using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull(NSG)mice.Tumor-bearing mice were divided into six treatment groups:no treatment,expanded NK cells(eNKs),Dara,Dara+eNKs,Dvd,and Dvd+eNKs.Dvd treatment strongly enhanced the cytotoxicity of eNKs by upregulating expression of NK cell activation ligands,downregulating expression of NK cell inhibitory ligands,and promoting antibody-dependent cellular cytotoxicity.The combination of eNKs with Dvd significantly prolonged mouse survival and reduced the tumor burden and serum M-protein level.Furthermore,Dvd pretreatment significantly increased eNK persistence and homing to MM sites.Our findings suggest that Dvd treatment potentiates the antimyeloma effects of NK cells expanded and activated ex vivo by modulating immune responses in MM-bearing mice.展开更多
基金supported by grants from the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(2018R1A5A2024181,2020R1A2C2010098).
文摘Nanovaccines are used as delivery platforms for antigens and adjuvants, which activate antigen-presenting cells (APCs) and enhance anticancer immune responses.1,2 Researchers have recently developed a self-assembled nanocomplex using a polysorbitol-co-PEI (PSPEI) polymer complexed with poly(I:C) (PIC). By binding to different surface proteins, this nanocomplex enhances the intracellular delivery of cargos and induces potent anticancer immune responses against melanoma cells.3 We have previously demonstrated that PD-1/PD-L1 blockade enhanced the efficacy of DC-based cancer immunotherapy.4,5 Moreover, the combination of nanomedicines and PD-L1 blockade has been reported to enhance CD8+ T cell activation and inhibit immunosuppressive cells within the tumor microenvironment.6 In the present study, we investigated the therapeutic efficacy of a combinatorial treatment comprising the immunoadjuvant nanocomplex PSPEI-PIC, a DC vaccine, and PD-L1 blockade in a murine colon cancer model.
基金supported by grants from the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(2018R1A2B6006200,2018R1A5A2024181,and 2020R1A2C2010098).
文摘The use of natural killer(NK)cells is a promising and safe immunotherapeutic approach in the field of cancer immunotherapy.However,combination treatments are required to enhance the effector functions and therapeutic efficacy of NK cells.In this study,we investigated the potential of daratumumab(Dara),bortezomib,and dexamethasone(Dvd)to augment the antitumor effects of NK cells in a multiple myeloma(MM)xenograft mouse model.NK cells were expanded and activated using the K562-OX40 ligand and membrane-bound IL-18 and IL-21 in the presence of IL-2 and IL-15 from peripheral blood mononuclear cells from MM patients.A human MM xenograft model was established using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγnull(NSG)mice.Tumor-bearing mice were divided into six treatment groups:no treatment,expanded NK cells(eNKs),Dara,Dara+eNKs,Dvd,and Dvd+eNKs.Dvd treatment strongly enhanced the cytotoxicity of eNKs by upregulating expression of NK cell activation ligands,downregulating expression of NK cell inhibitory ligands,and promoting antibody-dependent cellular cytotoxicity.The combination of eNKs with Dvd significantly prolonged mouse survival and reduced the tumor burden and serum M-protein level.Furthermore,Dvd pretreatment significantly increased eNK persistence and homing to MM sites.Our findings suggest that Dvd treatment potentiates the antimyeloma effects of NK cells expanded and activated ex vivo by modulating immune responses in MM-bearing mice.
