Use of Booster Inoculations to Sustain the Clinical Effect of an Adjuvant Breast Cancer Vaccine From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02

BACKGROUND: The authors are conducting clinical trials of the HER-2/neu E75-peptide vaccine in clinically disease-free breast cancer (BC) patients. Their phase 1-2 trials revealed that the E75 + granulocyte-macrophage colony-stimulating factor (GM-CSF) vaccine is safe and effective in stimulating clonal expansion of E75-specific CD8(+) T cells. They assessed the need for and response to a booster after completion of primary vaccination series. METHODS: BC patients enrolled in the E75 vaccine trials who were >= 6 months from completion of their primary vaccination series were offered boosters with E75 + GM-CSF. Patients were monitored for toxicity. E75-specific CD8(+) T cells were quantified using the human leukocyte antigen-A2: immunoglobulin G dimer before and after boosting. RESULTS: Fifty-three patients received the vaccine booster. Median time from primary vaccination series was 9 months (range, 6-35 months), and median residual E75-specific immunity was 0.70% (range, 0-3.49%) CD8(+) lymphocytes. Elevated residual immunity (ERI) (CD8(+) E75-specific T cells >0.5%) was seen in 94.4% of patients at 6 months from primary vaccination series versus 48% of patients at >6 months (P = .002). The booster was well tolerated, with only grade 1 and 2 toxicity observed. Local reactions were more robust in patients receiving the booster at 6 months from primary vaccination series compared with those at >6 months (99.4 +/- 6.1 mm vs 81.8 +/- 4.1 mm, P = .01). In patients lacking ERI, 85% had increased ERI after vaccination (P = .0014). CONCLUSIONS: The HER-2/neu E75 peptide vaccine E75 stimulates specific immunity in disease-free BC patients. However, immunity wanes with time. A vaccine booster is safe and effective in stimulating E75-specific immunity in those patients without ERI. These results suggest that the booster may be most effective at 6 months after completion of the primary vaccination series. Cancer 2011;117:463-71. Published 2010 by the American Cancer Society.*