Clinical and immunologic effects of a HER2/neu (E75) peptide vaccine booster in previously vaccinated breast cancer patients

Abstract

3014 Background: We are conducting clinical trials of the HER2/neu E75-peptide vaccine in clinically disease-free breast cancer (BCa) patients. Our Phase I/II trials have shown that the E75+GM-CSF vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8+ T-cells. Since peptide vaccines may not lead to long term immunity, we have assessed the need for and response to a vaccine booster for patients after completion of their primary vaccination series. Methods: BCa patients enrolled in our E75 vaccine trials who were >6 months from the completion of their primary vaccination series were offered a single 1000 mcg dose of E75 peptide with 250 mcg of GM-CSF. Patients were monitored for local and systemic toxicity. E75-specific CD8+ T-cells were quantified using the HLA-A2:IgG dimer before and after booster administration. Results: 19 patients have received the vaccine booster. Median time from primary vaccine series was 12 months (range 6–25) and median residual E75-specific immunity was 0.61% (range 0- 3.43%). Significant residual immunity (SRI=CD8+ E75-specific T-cells >0.5%) was seen in 71% of patients <12 months from primary vaccination vs. 33% of patients ≥12 months. Graded local toxicities were as follows: 18/19 (94.7%) grade 1; 1/19 (5.3%) grade 2. Only 6/19 (31.6%) experienced even grade 1 systemic toxicity. Local reactions were more robust in patients receiving the booster <12 months from primary vaccine compared to those ≥12 months (99±2.8 mm vs. 75±1 mm, p=0.01). In patients lacking SRI, 80% showed increased specific immunity post-vaccination. In these patients, the average CD8+ E75-specific T-cells pre-booster vs. post-booster was 0.37±0.03% vs. 1.06 ± 0.14% (p=0.07). Conclusions: The HER2/neu peptide vaccine E75 stimulates specific immunity in disease-free BCa patients. However, only about half of patients show SRI at median follow-up of 12 months. A vaccine booster is safe and highly effective in stimulating E75-specific immunity especially in those patients without SRI. Initial results suggest that the booster should be given within a year of completion of the initial vaccine series. No significant financial relationships to disclose.