The adjuvant effect of melanin is superior to incomplete Freund's adjuvant in subunit/peptide vaccines in mice
- 30 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 69 (12), 2501-2512
- https://doi.org/10.1007/s00262-020-02631-7
Abstract
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.This publication has 33 references indexed in Scilit:
- Persistent antigen at vaccination sites induces tumor-specific CD8+ T cell sequestration, dysfunction and deletionNature Medicine, 2013
- Type I IFNs Control Antigen Retention and Survival of CD8α+ Dendritic Cells after Uptake of Tumor Apoptotic Cells Leading to Cross-PrimingThe Journal of Immunology, 2011
- Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909Cancer Immunology, Immunotherapy, 2010
- Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II studyNeuro-Oncology, 2010
- Analyzing real-time PCR data by the comparative CT methodNature Protocols, 2008
- Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-primingProceedings of the National Academy of Sciences of the United States of America, 2007
- Constant rate of steady-state self-antigen trafficking from skin to regional lymph nodesInternational Immunology, 2006
- Combined TLR and CD40 Triggering Induces Potent CD8+ T Cell Expansion with Variable Dependence on Type I IFNThe Journal of Experimental Medicine, 2004
- Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-β1-dependent cellsInternational Immunology, 2001
- Exact prediction of a natural T cell epitopeEuropean Journal of Immunology, 1991