Cancer vaccine efficacy relies on T cells eliciting tumor-specific adaptive immunity,with antigen-presenting cells,particularly dendritic cells(DCs),playing a crucial role.After capturing antigens,DCs migrate to lymph...Cancer vaccine efficacy relies on T cells eliciting tumor-specific adaptive immunity,with antigen-presenting cells,particularly dendritic cells(DCs),playing a crucial role.After capturing antigens,DCs migrate to lymph nodes,where they present antigens to naïve T cells and activate B and natural killer(NK)cells,thereby strengthening anti-tumor immune responses.However,limitations in immune adjuvants and insufficient antigen presentation hinder DCs migration,reducing vaccine effectiveness.This study introduces an outer membrane vesicle(OMV)-based platform engineered to express Vibrio vulnificus flagellin B(FlaB),a Toll-like receptor 5(TLR5)agonist.FlaB effectively activates DCs,enhances interactions with T cells,provides robust costimulatory signals,and promotes cytotoxic CD8^(+)T cell differentiation.Compared to unmodified OMV-Ag,the antigen-loaded OMV-FlaB-Ag nanovaccine significantly enhances DC function,eliciting potent antitumor responses and delaying tumor progression across multiple models.When combined with immune checkpoint inhibitors,it further amplifies antitumor immunity,markedly suppressing tumor growth and improving therapeutic outcomes.展开更多
Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors i...Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.展开更多
基金supported by the National Natural Science Foundation of China(Nos.U24A20765 and T2321005)Jiangsu Provincial Science and Technology Plan Special Fund(No.BM2023003)+1 种基金Jiangsu Provincial Medical Key Discipline(No.ZDXK202247)the Priority Academic Program Development of the Jiangsu Higher Education Institutes.
文摘Cancer vaccine efficacy relies on T cells eliciting tumor-specific adaptive immunity,with antigen-presenting cells,particularly dendritic cells(DCs),playing a crucial role.After capturing antigens,DCs migrate to lymph nodes,where they present antigens to naïve T cells and activate B and natural killer(NK)cells,thereby strengthening anti-tumor immune responses.However,limitations in immune adjuvants and insufficient antigen presentation hinder DCs migration,reducing vaccine effectiveness.This study introduces an outer membrane vesicle(OMV)-based platform engineered to express Vibrio vulnificus flagellin B(FlaB),a Toll-like receptor 5(TLR5)agonist.FlaB effectively activates DCs,enhances interactions with T cells,provides robust costimulatory signals,and promotes cytotoxic CD8^(+)T cell differentiation.Compared to unmodified OMV-Ag,the antigen-loaded OMV-FlaB-Ag nanovaccine significantly enhances DC function,eliciting potent antitumor responses and delaying tumor progression across multiple models.When combined with immune checkpoint inhibitors,it further amplifies antitumor immunity,markedly suppressing tumor growth and improving therapeutic outcomes.
基金This work was partially supported by the National Natural Science Foundation of China(No.22077093)the National Research Programs from Ministry of Science and Technology(MOST)of China(Nos.2021YFF0701800 and 2022YFF0706500)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20220110)the Collaborative Innovation Center of Suzhou Nano Science and Technology,the Suzhou Key Laboratory of Nanotechnology and Biomedicine,and the 111 Program from the Ministry of Education of China。
文摘Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death.However,the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression.Herein,fluorinated CaCO_(3)(CaF)nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process.After being coated with commercial lipids and hexadecylamin conjugated chlorin e6(hCe6)via a templated self-assembly process,the yielded PEGylated nanophotosensitizer(hCe6@CaF-PEG)exhibits an effective loading efficiency to perfluoro-15-crown-5-ether(PFCE),a model perfluorocarbon molecule,and thus oxygen molecules.Upon intravenous administration,the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle.Together with local light emitting diode light exposure,photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors,particularly when synergized with anti-PD-1(aPD-1)immunotherapy to collectively reverse tumor immunosuppression.This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.
