Tumor therapy in mice by using a tumor antigen linked to modulin peptides from Staphylococcus epidermidis.
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.
Durantez
Maika
M
University of Navarra, Centre for Applied Medical Research (CIMA), Gene Therapy and Hepatology Area, Pamplona 31008, Spain.
Fayolle
Catherine
C
Casares
Noelia
N
Belsue
Virginia
V
Riezu-Boj
José I
JI
Sarobe
Pablo
P
Prieto
Jesús
J
Borrás-Cuesta
Francisco
F
Leclerc
Claude
C
Lasarte
Juan J
JJ
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology; D013212:Staphylococcus epidermidis; D051195:Toll-Like Receptor 2 / Q000276:immunology
D000951:Antigens, Neoplasm; D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; D050725:Papillomavirus E7 Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C059731:oncogene protein E7, Human papillomavirus type 16; C025971:staphylococcal delta toxin; D066246:ErbB Receptors; D011070:Poly I-C