Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer

Abstract

Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patients with advanced stage breast cancer to either treat minimal residual disease or prevent relapse. However, little is known concerning the incidence and magnitude of the pre-existent breast cancer specific immune response in this patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patients with advanced stage HER-2/neu overexpressing breast and ovarian cancers (III/IV) had evidence of pre-existent immunity to HER-2/neu. Forty-five patients with stage III or IV HER-2/neu overexpressing breast or ovarian cancer were evaluated for HER-2/neu specific T cell and antibody immunity. Patients enrolled had not received immunosuppressive chemotherapy for at least 30 days (median 5 months, range 1-75 months). All patients were documented to be immune competent prior to entry by DTH testing using a skin test anergy battery. Five of 45 patients (11%) were found to have a significant HER-2/neu specific T cell response as defined by a stimulation index > or = 2.0 (range 2.0-7.9). None of eight patients who were HLA-A2 had a detectable IFNgamma secreting T-cell precursor frequency to a well-defined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7%) had detectable HER-2/neu specific IgG antibodies, range 1.2-8.9 microg/ml. These findings suggest that patients with advanced stage HER-2/neu overexpressing breast and ovarian cancer can mount a T cell and/or antibody immune response to their tumor. However, in the case of the HER-2/neu antigen, the pre-existent tumor specific immune response is found only in a minority of patients.