Abstract
Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8–35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides. Immunization with melanin-bound peptides efficiently triggered CTL responses in mice, even against self-antigens and at a very low dose of peptides (microgram range). Immunization against a tumor antigen inhibited the growth of established tumors in mice, an effect that was abrogated by the depletion of CD8+ lymphocytes. These results demonstrate the efficacy of melanin as a vaccine adjuvant.
Highlights
The recent developments in the ability to identify genetic mutations that can be recognized by the immune system, along with the success of immune checkpoint inhibitors, have renewed the interest for cancer vaccines [1,2,3]
cytotoxic T- lymphocytes (CTLs) recognize short peptidic epitopes that result mainly from degraded intracellular proteins, and that are displayed by major histocompatibility complex (MHC) class I molecules on the surfaces of target cells and/or antigen
We investigated the ability of this formulation to trigger CTL responses with a self-epitope derived from the murine Ephrin-A2 protein (EphA2) and with a long synthetic peptide (30 amino acids) containing the classic ovalbumin SIINFEKL epitope
Summary
The recent developments in the ability to identify genetic mutations that can be recognized by the immune system (neo-epitopes), along with the success of immune checkpoint inhibitors, have renewed the interest for cancer vaccines [1,2,3]. Immunity in cancer is mainly mediated by cytotoxic T- lymphocytes (CTLs) [4,5]. CTLs recognize short peptidic epitopes (eight to ten amino acid residues) that result mainly from degraded intracellular proteins, and that are displayed by major histocompatibility complex (MHC) class I molecules on the surfaces of target cells and/or antigen. AF Carpentier & C Banissi are listed as inventors. This does not alter our adherence to PLOS ONE policies on sharing data and materials
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