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
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.