title: Induction of HER2 Immunity in Outbred Domestic Cats by DNA Electrovaccination.
abstract: Domestic cats share human living environments and genetic traits. They develop spontaneous feline mammary carcinoma (FMC) with similar histopathology to human breast cancer. HER2 and AKT phosphorylation was demonstrated in primary FMC by immunoblot analysis, indicating HER2 as a therapeutic target. FMC lines K12 and K248 expressing HER1, HER2, and HER3 were sensitive to receptor tyrosine kinase (RTK) inhibitors gefitinib and lapatinib. To test HER2 vaccine response in cats, purpose-bred, healthy cats were electrovaccinated with heterologous (xenogeneic) or point-mutated feline HER2 DNA. T-cell reactivity to feline self-HER2 was detected in 4 of 10 cats that received bear HER2, human-rat fusion HER2 (E2Neu) or mutant feline HER2 (feHER2-K), which contains a single amino acid substitution. The variable T-cell responses may resemble that in the genetically heterogeneous human population. All immune sera to heterologous HER2 recognized feline HER2 expressed in 3T3 cells (3T3/HER2), but not that in FMC K12 or K248. Immune sera to mutant pfeHER2-K bound 3T3/HER2 cells weakly, but they showed better recognition of K12 and K248 cells that also express HER1 and HER3, suggesting distinct HER2 epitopes displayed by FMC that may be simulated by feHER2-K. In summary, HER2 DNA electroporation overcomes T-cell immune tolerance in approximately 40% of healthy cats and induces antibodies with distinct specificity. Vaccination studies in domestic cats can expedite vaccine iteration to guide human vaccine design and better predict outcome, with the added benefit of helping feline mammary tumor patients.
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Gibson
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Veenstra
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Richard
authors.initials: R
authors.lastname: Jones
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.affiliation: Oakland Veterinary Referral Services, Bloomfield Hills, Michigan.
authors.forename: Michele
authors.initials: M
authors.lastname: Sauerbrey
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Gerold
authors.initials: G
authors.lastname: Bepler
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lum
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Joyce
authors.initials: J
authors.lastname: Reyes
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors.forename: Amy
authors.initials: A
authors.lastname: Weise
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan. weiw@karmanos.org.
authors.forename: Wei-Zen
authors.initials: WZ
authors.lastname: Wei
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002415:Cats; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018274:Electroporation; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D015674:Mammary Neoplasms, Animal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D001503:Ursidae; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C508053:ERBB2 protein, human