Supramolecular co-assembly of self-adjuvanting nanofibrious peptide hydrogel enhances cancer vaccination by activating MyD88-dependent NF-κB signaling pathway without inflammation

Peptide vaccine targeting tumor-specific antigens is a promising cancer treatment regimen.However,peptide vaccines are commonly low-immunogenic,leading to suboptimal antitumor T-cell responses.Current peptide vaccination approaches are challenged by the variability of peptide physicochemical characters and vaccine formulations,flexibility,and the broad feasibility.Here,the supramolecular co-assembly of antigen epitope-conjugated peptides(ECPs)targeting CD8 or CD4 T-cell receptors was used to engineer a nanofibrious hydrogel vaccine platform.This approach provided precise and tunable loading of peptide antigens in nanofibers,which notably increased the antigen uptake,cross-presentation,and activation of dendritic cells(DCs).Immunization in mice indicated that the co-assembled peptide hydrogel did not induce local inflammation responses and elicited significantly promoted T-cell immunity by activating the MyD88-dependent NF-κB signaling pathway in DCs.Vaccination of mice using co-assembled peptide vaccine stimulated both enhanced CD8 and CD4 T cells against EG.7-OVA tumors without additional immunoadjuvants or delivery systems,and resulted in a more remarkable cancer immunotherapy efficacy,compared with free peptide vaccine or aluminum-adjuvanted peptide formulation.Altogether,peptide co-assembly demonstrated by three independent pairs of ECPs is a facile,customizable,and chemically defined approach for co-delivering peptide antigens in self-adjuvanting hydrogel vaccines that could induce stronger anticancer T-cell responses.