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

Vaccine. 2010 Oct 18;28(44):7146-54. doi: 10.1016/j.vaccine.2010.08.070. Epub 2010 Sep 15.

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-2D(b)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Neoplasm / administration & dosage
  • Antigens, Neoplasm / immunology*
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / immunology*
  • Dendritic Cells / immunology
  • Epitopes, T-Lymphocyte / immunology
  • ErbB Receptors / metabolism
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / prevention & control
  • Papillomavirus E7 Proteins / administration & dosage
  • Papillomavirus E7 Proteins / immunology*
  • Poly I-C / immunology
  • Staphylococcus epidermidis
  • Toll-Like Receptor 2 / immunology

Substances

  • Antigens, Neoplasm
  • Bacterial Toxins
  • Epitopes, T-Lymphocyte
  • Papillomavirus E7 Proteins
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • oncogene protein E7, Human papillomavirus type 16
  • staphylococcal delta toxin
  • ErbB Receptors
  • Poly I-C