ErbB2 genetic cancer vaccine in nonhuman primates: relevance of single nucleotide polymorphisms.
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.
Fattori
Elena
E
Istituto di Ricerca di Biologia Molecolare, Via Pontina, Pomezia, Italy. Elena_fattori@merck.com
Aurisicchio
Luigi
L
Zampaglione
Immacolata
I
Arcuri
Mirko
M
Cappelletti
Manuela
M
Cipriani
Barbara
B
Mennuni
Carmela
C
Calvaruso
Francesco
F
Nuzzo
Maurizio
M
Ciliberto
Gennaro
G
Monaci
Paolo
P
La Monica
Nicola
N
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*
D011994:Recombinant Proteins; D019444:Vaccines, DNA