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

Citation
Ml. Disis et al., Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer, BREAST CANC, 62(3), 2000, pp. 245-252
Citations number
18
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BREAST CANCER RESEARCH AND TREATMENT
ISSN journal
01676806 → ACNP
Volume
62
Issue
3
Year of publication
2000
Pages
245 - 252
Database
ISI
SICI code
0167-6806(200008)62:3<245:PITTHO>2.0.ZU;2-L
Abstract
Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patien ts with advanced stage breast cancer to either treat minimal residual disea se or prevent relapse. However, little is known concerning the incidence an d magnitude of the pre-existent breast cancer specific immune response in t his patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patient s 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 pati ents 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. Patien ts 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 greater than or equal to 2.0 (range 2.0-7.9). None of eight patients who were HLA-A2 ha d a detectable IFN gamma secreting T-cell precursor frequency to a well-def ined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7%) h ad detectable HER-2/neu specific IgG antibodies, range 1.2-8.9 mu g/ml. The se findings suggest that patients with advanced stage HER-2/neu overexpress ing breast and ovarian cancer can mount a T cell and/or antibody immune res ponse to their tumor. However, in the case of the HER-2/neu antigen, the pr e-existent tumor specific immune response is found only in a minority of pa tients.