title: A cancer therapeutic vaccine based on clustered Tn-antigen mimetics induces strong antibody-mediated protective immunity.
abstract: Tumor-associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of vaccines based on native TACAs such as α-Tn have shown immunogenicity and protection in preclinical animal studies, however, their weak immunogenicity, low in vivo instability, and poor bioavailability, have discouraged their further evaluations in clinical studies. A new improved vaccine prototype is reported. It is composed of four clustered Tn-antigen mimetics and a immunogenic peptide epitope that are conjugated to a cyclopeptide carrier. The immunization of mice with this vaccine 1) was safe, 2) induced a strong and long-lasting Tn-specific response with IgM/IgG antibodies able to recognize native carbohydrate antigens; 3) produced high titers of IgG1, IgG2a, and IgG3 antibodies; and 4) produced a significant antibody-dependent regression of tumors and conferred protection. Altogether, these findings pave the way for the clinical development of safe and effective therapeutic vaccines against Tn-expressing cancers.
authors.affiliation: Department of Chemistry "Ugo Schiff", University of Florence via della Lastruccia, 13, 50019 Sesto F.no (FI) (Italy).
authors.forename: Barbara
authors.initials: B
authors.lastname: Richichi
authors.forename: Baptiste
authors.initials: B
authors.lastname: Thomas
authors.forename: Michele
authors.initials: M
authors.lastname: Fiore
authors.forename: Rosa
authors.initials: R
authors.lastname: Bosco
authors.forename: Huma
authors.initials: H
authors.lastname: Qureshi
authors.forename: Cristina
authors.initials: C
authors.lastname: Nativi
authors.forename: Olivier
authors.initials: O
authors.lastname: Renaudet
authors.forename: Lbachir
authors.initials: L
authors.lastname: BenMohamed
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; C040286:Tn antigen
keywords: Tn antigen; antitumor agents; cancer; immunology; synthetic vaccines