Self-assembling peptide epitopes for tumor vaccination

INTRODUCTION Synthetic peptide epitopes show promise as a personalized cancer vaccine but suffer from poor cellular uptake, processing and adequate immune activation. We have designed a small self-assembling peptide tag that-when appended to soluble peptide epitopes-forms discrete nanovesicles. The objective of this study was to show the immunopotentiating effect of such selfassembling peptide epitopes (SAPE) in a tumor vaccination study in mice. MATERIALS AND METHODS The self-assembling peptide domain (AcAAVVLLLW-COOH) was appended to the N-terminus of three different T-cell epitopes (OVA250-264, OVA317-339, HPV E743-57) to generate self-assembling peptide epitopes (SAPEs). The SAPE nanostructures were characterized by atomic force microscopy (AFM), and dynamic light scattering (DLS). SAPEs were subsequently tested in C57BL/6 mice to induce tumor-specific T-cell responses in both a prophylactic as well as therapeutic (mice bearing s.c. TC-1 or B16-OVA tumors) vaccination regimen. RESULTS AND DISCUSSION SAPE bearing either OVA or HPV epitopes formed discrete nanostructures of 30-90 nm in size (Fig. 1). Small differences in the selfassembling behaviour were observed for different peptide epitopes. Nanoparticles remained stable for up to a month when stored at 4 °C. It was also shown that the SAPEs adjuvanted with CpG were able to induce and expand specific CD8+ and CD4+ T cells in C57BL/6 mouse models. Furthermore, vaccination with HPV-SAPE showed partial TC-1 tumor regression with an increased survival proportion of mice compared to soluble HPV peptide vaccines (Fig. 2). CONCLUSIONS The extension of soluble, minimal T cell epitopes by a self-assembling domain can efficiently augment the induction of an antitumor immune response, first, by risk reduction of T cell anergy and second, by enhancing cellular uptake through particle formation.