Cancer immunotherapy is a new paradigm of cancer treatment in which the patient’s immune cells are reprogrammed to treat the body’s own cancer. In our lab, previous studies of gold nanoparticle (AuNP) cancer vaccines (AuNV) have successfully elicited an immune response in vivo using AuNVs with a proof of concept antigen. Surprisingly, those studies showed that delivery of known adjuvants with the AuNVs did not improve the overall immune response, prompting the question if the AuNVs themselves could elicit adjuvant responses. In this work, the primary objective is to determine if modified AuNVs induce IL-12 cytokine production in bone marrow derived cells (BMDCs) extracted from C57BL6/J mice. Previous work conducted by Yang et. al demonstrated that aromatic amino acid-terminated peptides on the surface of gold nanoparticles improved cellular uptake. We hypothesized that aromatic amino acid-terminated AuNVs could have improved uptake, which could potentially lead to more cytokine release by dendritic cells. We tested this hypothesis by synthesizing variations of the GP100 peptide (KVPRNQDWL) in which the terminal leucine residue was substituted with an aromatic residue. The peptides were conjugated to PEGylated AuNPs via EDC/Sulfo-NHS coupling chemistry. After completing the synthesis, the AuNV variants were incubated with BMDCs harvested from naïve mice and the induced IL-12 cytokine production was measured via an ELISA assay. According to Xia et. al (2012), IL-12 is one of the most prominent cytokines involved in activating Th1 cells, which are immune cells involved in attacking foreign substances in the body. AuNVs with aromatic gp100 peptides produced no discernable trend with regard to IL-12 cytokine production. However, AuNPs conjugated with modified PEG induced higher levels of IL-12 than AuNPs conjugated with methylated PEG. In the future, we intend to investigate this trend further by conducting additional ELISAs. We will also conduct flow cytometry with anti-CD40, anti-CD80, and anti-CD86 cell surface markers, which are indicative of immune activation in dendritic cells. If further research demonstrates AuNVs can elicit a sufficient immune response without requiring administration of an additional adjuvant, the clinical administration of cancer vaccines would be simplified.

Investigation of the effect of AuNVs conjugated with modified gp100 peptide and with modified PEG on induced IL-12 cytokine production

253rd National Meeting (2017)

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