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1826
Analysis of HER-2/neu (HER2) Specific Antibody
Immunity Generated in Patients with HER2 Expressing Cancers
Following Immunization with Peptide-Based Vaccines. Vivian j.
Goodell, Kathy S. Schiffman, Mary L. Disis, Univ of Washington,
Seattle, WA.
Sixty-four patients with Stage III or IV HER2 overexpressing
breast (n=53), ovarian (n=9), or non-small cell lung cancer (n=2)
were enrolled in a Phase I study of HER2 peptide-based vaccines.
Subjects received interdermal vaccinations monthly for 6 months with
1 of 3 peptide-based vaccine formulations admixed with GM-CSF as an
adjuvant. The development of HER2 antibody immunity was assessed.
55% (n=35) patients developed antibody responses to HER2 peptides,
range 0.86-21.6 ug/ml, as measured by ELISA. Positive responses were
defined as the mean and 3 standard deviations of a volunteer donor
control population (n=56, 0.07+/-0.26 ug/ml). Antibody responses to
the HER2 protein were detected in 25% (n=16) of patients, range
1.2-9.6 ug/ml, mean 4.1 and median 2.5 ug/ml. Positive responses
were defined as the mean and 2 standard deviations of a volunteer
donor control population (n=157, 0.20+/-0.4 ug/ml). The presence of
HER2 antibodies by ELISA was validated by Western blot analysis.
Patients with HER2 overexpressing cancers have been reported to have
a pre-existent HER2 protein antibody response, and indeed, 5 of the
16 patients had detectable HER2 specific antibodies prior to
immunization (8% of the total enrolled population). In 2 of the 5,
antibody immunity was boosted during vaccination, in 3 of the 5
there was no change in the level of HER2 antibodies with
immunization. In 11 of 16 the HER2 antibody response developed only
after immunization, therefore, antibodies to the HER2 protein were
generated by immunization in 20% (n=13) of the population
vaccinated. The HER2 specific protein antibodies detected were IgG,
only one patient had significant levels of IgA HER2 antibody and
that response pre-dated vaccination. Subclass analysis revealed a
predominant IgG1 component.
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