Biodegradable Microneedle Patch Delivering Antigenic Peptide-Hyaluronate Conjugate for Cancer Immunotherapy

Abstract

Antigenic peptide-delivery systems have been extensively investigated to harness the immune system for cancer therapy. Cytotoxic T-cell epitope peptide can induce an antigen-specific CD8(+) T-cell response, which subsequently inhibits the growth of antigen-bearing tumors. However, there are only a few facile tailored delivery systems of antigenic peptide for effective cancer immunotherapy. Here, we developed a biodegradable microneedle patch delivering a hyaluronate (HA)-antigenic peptide conjugate for prophylactic cancer immunotherapy. Cytotoxic T-cell epitope peptide (SIINFEKL) was conjugated to HA, which was loaded into a biodegradable HA microneedle (MN) patch to efficiently deliver an antigen to the immune system in the skin. HA could act as a transdermal vaccine carrier eliciting strong immune responses by the efficient stimulation of immunocompetent cells. The HASIINFEKL conjugates loaded into biodegradable MNs were localized near the MN administration site, exhibiting long-term residence for more than 24 h post-administration. Remarkably, a single transdermal vaccination with the MN patch containing HA-SIINFEKL conjugates resulted in a statistically significant inhibition of tumor growth in B16 melanoma model mice by enhancing antigen-specific cytotoxic T-cell responses.