In vivo Gold Nanoparticle Delivery of Peptide Vaccine Induces Anti‐Tumor Immune Response in Prophylactic and Therapeutic Tumor Models

Abstract

Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, we hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16-OVA tumor model. AuNP delivery of OVA (AuNP-OVA) and of CpG (AuNP-CpG) enhanced the efficacy of both agents and induced strong antigen-specific responses. In addition, we found that AuNP-OVA delivery alone, without CpG, was sufficient to promote significant antigen-specific responses, leading to subsequent anti-tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy was likely due to the adjuvant effect of peptide coated AuNPs, as they induced inflammatory cytokine release when cultured with bone marrow dendritic cells. Overall, we demonstrate that AuNP mediated OVA peptide delivery can produce significant therapeutic benefit without the need of adjuvant, indicating that AuNPs are effective peptide vaccine carriers with the potential to permit the use of lower and safer adjuvant doses during vaccination.

Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity

“…Notably, configurations where either IL-15:IL-15R␣ or OVA was detached from the NPs did not enhance animal sur- vival beyond the control group. Our findings align with recent literature showing that OVA vaccination requires an adjuvant to potentiate antigen-specific protective immunity (97)(98)(99)(100) and further highlight the importance of adjuvant configuration in the case of IL-15. Overall, we show that nanoparticles transpresenting IL-15:IL-15R␣ and encapsulating antigen demonstrate in vivo efficacy in the treatment of an aggressive model of murine melanoma.…”

Nanoparticle-Based Manipulation of Antigen-Presenting Cells for Cancer Immunotherapy

“…Two different nanoparticles of similar size, which experience similar pharmacokinetics, such as ultra‐small CpG nanoparticles injected alongside ultra‐small OVA conjugated nanoparticles, can also greatly enhance efficacy compared to only antigen‐loaded particles . A similar strategy has also been reported using co‐administered AuNPs conjugated with either CpG or OVA …”

Vaccine technologies: From whole organisms to rationally designed protein assemblies

“…Successful, preclinical vaccine candidates have been developed for diseases such as influenza, West Nile Virus, and plague [135][136][137]. There has also been interest and initial studies on the development of both prophylactic and therapeutic cancer vaccines based off of AuNP [138,139]. Despite the fact that AuNP can be easily modified into the most immunogenic shape and size in all published studies an external adjuvant needed to be added to generate a protective or effective vaccine candidate.…”