title: Airway administration of a highly versatile peptide-based liposomal construct for local and distant antitumoral vaccination.
abstract: With the discovery of tumor-associated antigens such as ErbB2, vaccination is considered as a promising strategy to prevent the development of cancer or treat the existing disease. Among routes of immunization, the respiratory route provides the opportunity to develop non-invasive approach for vaccine delivery. In the current study, this administration route was used in order to investigate the potency of a highly versatile di-epitopic liposomal construct to exhibit local or distant antitumoral efficiency after prophylactic or therapeutic vaccination in mice. Well-characterized liposomes, containing the ErbB2 (p63-71) TCD8(+) and HA (p307-319) TCD4(+) peptide epitopes and the Pam2CAG adjuvant, were formulated and administered into the airway of naïve BALB/c mice. The nanoparticle vaccine candidate induced local and specific systemic immune response, as measured by immune cell infiltration and chemokine and cytokine production in BALF or lung tissue, and by spleen T-cell activation ex vivo, respectively. This potent immune response resulted in an efficient antitumor activity against both lung and solid s.c. tumors. Interestingly, the antitumor efficacy was observed after both prophylactic and therapeutic vaccinations, which are the most judicious ones to fight cancer. Our data showed an undeniable interest of liposomal peptide-based vaccines in antitumor vaccination by the respiratory route, opening new perspectives for cancer treatment.
authors.affiliation: Equipe de Biovectorologie, Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199CNRS/Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch Cedex, France.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kakhi
authors.affiliation: Equipe de Biovectorologie, Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199CNRS/Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch Cedex, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Frisch
authors.affiliation: Equipe de Biovectorologie, Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199CNRS/Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch Cedex, France.
authors.forename: Line
authors.initials: L
authors.lastname: Bourel-Bonnet
authors.affiliation: Inserm UMR_S 1121, 11 rue Humann, 67085 Strasbourg, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hemmerlé
authors.affiliation: Equipe de Biovectorologie, Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199CNRS/Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch Cedex, France. Electronic address: pons@unistra.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Pons
authors.affiliation: Equipe de Biovectorologie, Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199CNRS/Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch Cedex, France. Electronic address: bheurtault@unistra.fr.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Heurtault
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008081:Liposomes; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D010455:Peptides / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D007371:Interferon-gamma; D008081:Liposomes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Cancer; Liposome; Mucosal immunization; Peptide-based vaccine; Respiratory route; Vaccination