title: ErbB2 genetic cancer vaccine in nonhuman primates: relevance of single nucleotide polymorphisms.
abstract: Aberrant Her2/neu expression is associated with the development of epithelial-derived human carcinomas and for this reason it is considered a good target for immunologic intervention. To define methods to circumvent immunologic tolerance and to elicit immunity against the Her2/neu tumor-associated antigen in a suitable animal model, we have isolated the cDNA encoding the rhesus monkey homolog of human Her2/neu (RhErbB2) to construct DNA plasmids and adenoviral vectors for the development of a cancer vaccine against this protein. To further increase the immunogenic potency of these vectors, a synthetic codon-optimized RhErbB2 cDNA (RhErbB2OPT) was constructed and characterized. Genetic vaccination of rhesus monkeys was effective in inducing a response against RhErbB2 in immunized animals; importantly, the elicited immunity was associated with natural RhErbB2 polymorphisms, thus distinguishing responses against "self " and "nonself " epitopes. In particular, the postpriming response recognized mainly nonself epitopes whereas the boosted response cross-reacted with self epitopes. Our findings are particularly relevant in the investigation of the impact of TAA polymorphisms on the efficacy of a cancer vaccine strategy.
authors.affiliation: Istituto di Ricerca di Biologia Molecolare, Via Pontina, Pomezia, Italy. Elena_fattori@merck.com
authors.forename: Elena
authors.initials: E
authors.lastname: Fattori
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
authors.forename: Immacolata
authors.initials: I
authors.lastname: Zampaglione
authors.forename: Mirko
authors.initials: M
authors.lastname: Arcuri
authors.forename: Manuela
authors.initials: M
authors.lastname: Cappelletti
authors.forename: Barbara
authors.initials: B
authors.lastname: Cipriani
authors.forename: Carmela
authors.initials: C
authors.lastname: Mennuni
authors.forename: Francesco
authors.initials: F
authors.lastname: Calvaruso
authors.forename: Maurizio
authors.initials: M
authors.lastname: Nuzzo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Paolo
authors.initials: P
authors.lastname: Monaci
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008253:Macaca mulatta; D051379:Mice; D008969:Molecular Sequence Data; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000276:immunology / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000096:biosynthesis; D017634:Self Tolerance; D017422:Sequence Analysis, DNA; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D019444:Vaccines, DNA