Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacl...Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacles include insufficient antigen loading and off-target to DCs remain to their success.Here,we developed an imageable therapeutic vaccine with whole-antigen loading and target delivery constructed by ovalbumin(OVA)-biomineralized Bi_(2)S_(3) nanoparticles-pulsed DCs.Relying on the strong X-ray absorption and fluorescence labeling performance of Bi_(2)S_(3)@OVA nanoparticles,the in vivo spatiotemporal fate of the vaccine(Bi_(2)S_(3)@OVA@DC)can be noninvasively monitored by computed tomography and near-infrared fluorescence imaging in real time.The Bi_(2)S_(3)@OVA@DC can rapidly and durably accumulate in draining lymph nodes and thus trigger stronger T-cell responses compared to OVA-pulsed DCs.Meanwhile,Bi_(2)S_(3)@OVA@DC can further achieve in vivo antitumor effects against OVA-expressing B16F10 melanoma when combined with fractionated radiotherapy,resulting from the upregulation of cytotoxic CD8^(+)T cells and restraint of regulatory T cells in the tumor microenvironment,and the systemical secretion of OVA-specific IgG1/IgG2α antibody.Overall,we successfully fabricated an engineered DC vaccine featured in high whole-antigen loading capacity that can be precisely delivered to the lymphatic system for visualization,serving as a powerful therapeutic platform for cancer radioimmunotherapy.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:22122407,12175162,32171403,12075164,31971319,21874097National Key Research Program of China,Grant/Award Number:2018YFA0208800+1 种基金Tang Scholar ProgramScientific Research Program for Young Talents of China National Nuclear Corporation and A Priority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Therapeutic vaccines,an exciting development in cancer immunotherapy,share the goal of priming of personalized antigen-specific T-cell response by precise antigen presentation of dendritic cells(DCs),but major obstacles include insufficient antigen loading and off-target to DCs remain to their success.Here,we developed an imageable therapeutic vaccine with whole-antigen loading and target delivery constructed by ovalbumin(OVA)-biomineralized Bi_(2)S_(3) nanoparticles-pulsed DCs.Relying on the strong X-ray absorption and fluorescence labeling performance of Bi_(2)S_(3)@OVA nanoparticles,the in vivo spatiotemporal fate of the vaccine(Bi_(2)S_(3)@OVA@DC)can be noninvasively monitored by computed tomography and near-infrared fluorescence imaging in real time.The Bi_(2)S_(3)@OVA@DC can rapidly and durably accumulate in draining lymph nodes and thus trigger stronger T-cell responses compared to OVA-pulsed DCs.Meanwhile,Bi_(2)S_(3)@OVA@DC can further achieve in vivo antitumor effects against OVA-expressing B16F10 melanoma when combined with fractionated radiotherapy,resulting from the upregulation of cytotoxic CD8^(+)T cells and restraint of regulatory T cells in the tumor microenvironment,and the systemical secretion of OVA-specific IgG1/IgG2α antibody.Overall,we successfully fabricated an engineered DC vaccine featured in high whole-antigen loading capacity that can be precisely delivered to the lymphatic system for visualization,serving as a powerful therapeutic platform for cancer radioimmunotherapy.
