Although powerful adjuvants hold promise of vaccines for cancer immunotherapy， cumbersome preparation processes， elusive mechanisms and failure to induce T cell responses have largely limited their clinical translation. Due to their ease of synthesis， good biocompatibility and designable bioactivity， peptide derivatives-based supramolecular nanomaterials have attracted increasing interest in improving the immunogenicity of cancer vaccines. : Herein， we synthesized an NF-κB-activating supramolecular nanoadjuvant (3DSNA) that is prepared by pH-triggering self-assembly of a positively charged D-configurational peptide derivative. The immunostimulatory activity of 3DNSA was explored and . : 3DSNA can st... More
Although powerful adjuvants hold promise of vaccines for cancer immunotherapy， cumbersome preparation processes， elusive mechanisms and failure to induce T cell responses have largely limited their clinical translation. Due to their ease of synthesis， good biocompatibility and designable bioactivity， peptide derivatives-based supramolecular nanomaterials have attracted increasing interest in improving the immunogenicity of cancer vaccines. : Herein， we synthesized an NF-κB-activating supramolecular nanoadjuvant (3DSNA) that is prepared by pH-triggering self-assembly of a positively charged D-configurational peptide derivative. The immunostimulatory activity of 3DNSA was explored and . : 3DSNA can strongly absorb the model antigen (ovalbumin， OVA) through electrostatic interaction. Then， 3DSNA promotes ingestion and cross-presentation of OVA， upregulation of costimulatory factors (CD80 and CD86) and secretion of proinflammatory cytokines (IL-6 and IL-12) by dendritic cells (DCs)， accompanied by activation of the innate immune response (NF-κB signaling)， resulting in long-term antigen-specific memory and effector CD8 T cells response. When compared with conventional aluminum hydroxide adjuvant and the corresponding L-configurational supramolecular nanoadjuvant (3LSNA)， 3DSNA-adjuvanted OVA (3DSNA+OVA) significantly prevents oncogenesis in naïve mice with a complete response rate of 60 %， restrains the tumor growth and prolongs the survival of melanoma-bearing mice. : These findings demonstrate that 3DSNA is a promising neo-adjuvant that enables various vaccines to be therapeutic for many important diseases including cancer.
