Activating humoral and cellular immunity in lymph nodes(LNs)of nanoparticle-based vaccines is critical to controlling tumors.However,how the physical properties of nanovaccine carriers orchestrate antigen capture,lymp...Activating humoral and cellular immunity in lymph nodes(LNs)of nanoparticle-based vaccines is critical to controlling tumors.However,how the physical properties of nanovaccine carriers orchestrate antigen capture,lymphatic delivery,antigen presentation and immune response in LNs is largely unclear.Here,we manufactured gold nanoparticles(AuNPs)with the same size but different shapes(cages,rods,and stars),and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas.Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes.On lymphatic delivery,both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention.A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity,which is mediated by CD4^(+)T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study.Interestingly,cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8^(+)T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study.These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs,and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.展开更多
Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the ...Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone.Herein,we proposed a trinity immune enhancing nanoparticles(TIENs)for boosting antitumor immune responses of chemo agents.The TIENs was constructed with Food and Drug Administration(FDA)approved polylactic acid(PLA),canonical proton-sponging cationic polymer polyethyleneimine(PEI),and Toll-like receptor 9(TLR9)agonist cytosine phosphate guanine oligodeoxynucleotide(CpG-ODN).In in vitro studies,the TIENs was proved to(1)promote antigen capturing,(2)antigen-presenting cells(APCs)activation,and(3)antigen cross-presentation.In in vivo studies,intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models,respectively.Furthermore,after decoration with a detachable shielding,the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection.The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81901878,U1804183,and 82202318)Key Scientific Research Project(Education Department of Henan Province,China,20HASTIT049)China Postdoctoral Science Foundation(2019M662553,2020T130611,and 2022TQ0310)。
文摘Activating humoral and cellular immunity in lymph nodes(LNs)of nanoparticle-based vaccines is critical to controlling tumors.However,how the physical properties of nanovaccine carriers orchestrate antigen capture,lymphatic delivery,antigen presentation and immune response in LNs is largely unclear.Here,we manufactured gold nanoparticles(AuNPs)with the same size but different shapes(cages,rods,and stars),and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas.Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes.On lymphatic delivery,both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention.A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity,which is mediated by CD4^(+)T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study.Interestingly,cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8^(+)T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study.These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs,and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.
基金supported by the National Natural Science Foundation of China(Nos.51973215,52025035,52003268,51829302,and 51833010)Bureau of International Cooperation Chinese Academy of Sciences(No.121522KYSB20200029)+1 种基金the Jilin Province Science and Technology Development Plan(No.2020122331JC)support from the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2020232).
文摘Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone.Herein,we proposed a trinity immune enhancing nanoparticles(TIENs)for boosting antitumor immune responses of chemo agents.The TIENs was constructed with Food and Drug Administration(FDA)approved polylactic acid(PLA),canonical proton-sponging cationic polymer polyethyleneimine(PEI),and Toll-like receptor 9(TLR9)agonist cytosine phosphate guanine oligodeoxynucleotide(CpG-ODN).In in vitro studies,the TIENs was proved to(1)promote antigen capturing,(2)antigen-presenting cells(APCs)activation,and(3)antigen cross-presentation.In in vivo studies,intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models,respectively.Furthermore,after decoration with a detachable shielding,the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection.The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.
