Peptide vaccines represent an attractive alternative to conventional anti-
tumor therapies, but have not yet achieved significant clinical efficacy with commonly used formulations. Combination of short antigenic
peptides, synthetic
melanin and TLR9
agonist (Toll-like receptor 9, CpG-28) was reported as highly efficient to trigger strong CD8 + T-cell responses. We compared this
vaccine approach to the standard adjuvant formulation that combines the
incomplete Freund's adjuvant (IFA) and CpG-28, using either an
ovalbumin epitope (pOVA30) or a spontaneously occurring
tumor neoepitope (mAdpgk).
Melanin-based
vaccine induced significantly higher cytotoxic T lymphocytes (CTL) responses than IFA-based
vaccine in both pOVA30- and mAdpgk-targeted
vaccines. The anti-
tumor efficacy of
melanin-based
vaccine was further assessed in mice, grafted either with E.G7-OVA cells (E.G7 cells transfected with
ovalbumin) or with MC38 cells that spontaneously express the mAdpgk neoepitope.
Melanin-based
vaccine induced a major inhibition of E.G7-OVA
tumor growth when compared to IFA-based
vaccine (p < 0.001), but
tumors eventually relapsed from day 24. In the MC38
tumor model, no significant inhibition of
tumor growth was observed. In both cases, tumor escape appeared related to the loss of antigen presentation by
tumor cells (loss of
ovalbumin expression in E.G7-OVA model; poor presentation of mAdpgk in MC38 model), although the CTL responses displayed an effector memory phenotype, a high cytolytic potential and low programmed cell death-1 (PD1) expression.In conclusion, synthetic
melanin can be efficiently used as an adjuvant to enhance T-cells response against
subunit vaccine antigens and compared favorably to the classic combination of IFA and TLR9 agonist in mice.