title: 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.
abstract: 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.
authors.affiliation: Department of Hematology and Medical Oncology, Naval Medical Center San Diego, San Diego, California, USA.
authors.forename: Jarrod P
authors.initials: JP
authors.lastname: Holmes
authors.forename: Guy T
authors.initials: GT
authors.lastname: Clifton
authors.forename: Ritesh
authors.initials: R
authors.lastname: Patil
authors.forename: Linda C
authors.initials: LC
authors.lastname: Benavides
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Gates
authors.forename: Alexander
authors.initials: A
authors.lastname: Stojadinovic
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mittendorf
authors.forename: Sathibalan
authors.initials: S
authors.lastname: Ponniah
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects; D007372:Interferons / Q000032:analysis; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D013997:Time Factors; D022223:Vaccines, Subunit / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D007372:Interferons; D018719:Erb-b2 Receptor Tyrosine Kinases; D022223:Vaccines, Subunit