In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire.However,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity sca...In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire.However,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity.To break this plight,a tumor-activated and optically reinforced immunoscaffold(TURN)is exploited to trigger cancer immunoediting phases regression,thus levering potent systemic antitumor immune responses.Upon response to tumoral reactive oxygen species,TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines,and thus immunosuppression falls and immunogenicity rises.Subsequently,intermittent laser irradiation-activated photothermal agents(PL)trigger abundant tumor antigens exposure,which causes immunogenicity springs and preliminary infiltration of T cells.Finally,CD137 agonists from TURN further promotes the proliferation,function,and survival of T cells for durable antitumor effects.Therefore,cancer immunoediting phases reverse and systemic antitumor immune responses occur.TURN achieves over 90%tumor growth inhibition in both primary and secondary tumor lesions,induces potent systemic immune responses,and triggers superior long-term immune memory in vivo.Taken together,TURN provides a prospective sight for ISV from the perspective of immunoediting phases.展开更多
基金supported by Funds of Sichuan Province for Distinguished Young Scholar(2021JDJQ0037)the National Natural Science Foundation of China(82372123)+1 种基金Central Guide Local Science and Technology Development Special Project fund(2023FRD05038)1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYYC23004).
文摘In situ vaccine(ISV)is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire.However,its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity.To break this plight,a tumor-activated and optically reinforced immunoscaffold(TURN)is exploited to trigger cancer immunoediting phases regression,thus levering potent systemic antitumor immune responses.Upon response to tumoral reactive oxygen species,TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines,and thus immunosuppression falls and immunogenicity rises.Subsequently,intermittent laser irradiation-activated photothermal agents(PL)trigger abundant tumor antigens exposure,which causes immunogenicity springs and preliminary infiltration of T cells.Finally,CD137 agonists from TURN further promotes the proliferation,function,and survival of T cells for durable antitumor effects.Therefore,cancer immunoediting phases reverse and systemic antitumor immune responses occur.TURN achieves over 90%tumor growth inhibition in both primary and secondary tumor lesions,induces potent systemic immune responses,and triggers superior long-term immune memory in vivo.Taken together,TURN provides a prospective sight for ISV from the perspective of immunoediting phases.
