Tumor therapy in mice by using a tumor antigen linked to modulin peptides from Staphylococcus epidermidis

• Published in: Vaccine 2010-10, Vol.28 (44), p.7146-7154
• Main Authors: Durantez, Maika, Fayolle, Catherine, Casares, Noelia, Belsue, Virginia, Riezu-Boj, José I, Sarobe, Pablo, Prieto, Jesús, Borrás-Cuesta, Francisco, Leclerc, Claude, Lasarte, Juan J
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antigen Presentation; Antigen targeting; Antigens, Neoplasm - administration & dosage; Antigens, Neoplasm - immunology; Applied microbiology; Bacterial Toxins - administration & dosage; Bacterial Toxins - immunology; Bacteriology; Biological and medical sciences; Cytotoxicity; Dendritic cells; Dendritic Cells - immunology; Epidermal growth factor; Epitopes, T-Lymphocyte - immunology; Female; Flow cytometry; Fundamental and applied biological sciences. Psychology; Gram-positive bacteria; Immune system; Ligands; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Miscellaneous; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - prevention & control; Papillomavirus E7 Proteins - administration & dosage; Papillomavirus E7 Proteins - immunology; Peptides; Phenols; Poly I-C - immunology; Polypeptides; Receptor, Epidermal Growth Factor - metabolism; Staphylococcus epidermidis; T-cells; Toll-Like Receptor 2 - immunology; Tumors; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.08.070

Abstract Staphylococcus epidermidis releases a complex of at least four peptides, termed phenol-soluble modulins (PSM), which stimulate macrophages to produce proinflammatory cytokines via activation of TLR2 signalling pathway. We demonstrated that covalent linkage of PSM peptides to an antigen facilitate its capture by dendritic cells and, in combination with different TLR ligands, can favour the in vivo induction of strong and persistent antigen-specific immune responses. Treatment of mice grafted with HPV16-E7-expressing tumor cells (TC-1) with poly(I:C) and a peptide containing αMod linked to the H-2Db -restricted cytotoxic T-cell epitope E7(49–57) from HPV16-E7 protein allowed complete tumor regression in 100% of the animals. Surprisingly, this immunomodulatory property of modulin-derived peptides was TLR2 independent and partially dependent upon the EGF-receptor signalling pathway. Our results suggest that alpha or gamma modulin peptides may serve as a suitable antigen carrier for the development of anti-tumoral or anti-viral vaccines.