title: Engineered CCR5 superagonist chemokine as adjuvant in anti-tumor DNA vaccination.
abstract: Chemokine receptors are promising targets for enhancing T-cell immunity and anti-cancer therapy. CCL5 is a potential adjuvant for DNA vaccination. We postulated that CCR5 superagonists could be even more effective. A CCR5 superagonist derived from natural CCL5 by directed in vitro evolution, namely 1P7, is used as a DNA vaccine adjuvant and expressed as fused chemokine-Ig (1P7-Ig). We show that OVA+1P7-Ig DNA co-inoculation induced higher frequencies of OVA-specific CD8 lymphocytes than OVA+CCL5-Ig or controls and gave an even better protection against tumor growth in a CCR5-dependant manner. Our results indicate that CCR5-superagonists may provide potent adjuvants for vaccines.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U543, Paris, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Dorgham
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Iga
authors.forename: Oliver
authors.initials: O
authors.lastname: Hartley
authors.forename: Guy
authors.initials: G
authors.lastname: Gorochov
authors.forename: Behazine
authors.initials: B
authors.lastname: Combadière
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D019713:Receptors, CCR5 / Q000819:agonists*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D018946:Chemokine CCL5; D019713:Receptors, CCR5; D019444:Vaccines, DNA; D010047:Ovalbumin