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, indicating HER2 as a therapeutic target. FMC lines K12 and K248 expressing HER1, 2 and 3 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 self feline 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 FMC K12 or K248. Immune sera to mutant pfeHER2-K bound 3T3/HER2 cells weakly, but they better recognized K12 and K248 cells that also express HER1 and 3, 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 ~40% 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.
- Received September 19, 2014.
- Revision received January 22, 2015.
- Accepted February 14, 2015.
- Copyright © 2015, American Association for Cancer Research.