title: Effect of dose on immune response in patients vaccinated with an her-2/neu intracellular domain protein--based vaccine.
abstract: OBJECTIVE
  To evaluate the safety of an HER-2/neu intracellular domain (ICD) protein vaccine and to estimate whether vaccine dose impacts immunogenicity.
  
  
  METHODS
  Twenty-nine patients with HER-2/neu-overexpressing breast or ovarian cancer and with no evidence of disease after standard therapy received a low- (25 microg), intermediate- (150 microg), or high-dose (900 microg) HER-2/neu ICD protein vaccine. The vaccine was administered intradermally, monthly for 6 months, with granulocyte-macrophage colony-stimulating factor as an adjuvant. Toxicity and both cellular and humoral HER-2/neu-specific immunity was evaluated.
  
  
  RESULTS
  The vaccine was well tolerated. The majority of patients (89%) developed HER-2/neu ICD-specific T-cell immunity. The dose of vaccine did not predict the magnitude of the T-cell response. The majority of patients (82%) also developed HER-2/neu-specific immunoglobulin G antibody immunity. Vaccine dose did not predict magnitude or avidity of the HER-2/neu-specific humoral immune response. Time to development of detectable HER-2/neu-specific immunity, however, was significantly earlier for the high- versus low-dose vaccine group (P =.003). Over half the patients retained HER-2/neu-specific T-cell immunity 9 to 12 months after immunizations had ended.
  
  
  CONCLUSIONS
  The HER-2/neu ICD protein vaccine was well tolerated and effective in eliciting HER-2/neu-specific T-cell and antibody immunity in the majority of breast and ovarian cancer patients who completed the vaccine regimen. Although the dose of vaccine did not impact the magnitude of T-cell or antibody immunity elicited, patients receiving the highest dose developed HER-2/neu-specific immunity more rapidly than those who received the lowest dose.
authors.affiliation: Tumor Vaccine Group, Oncology, University of Washington, Seattle, WA 98195-6527, USA. ndisis@u.washington.edu
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.forename: Kathy
authors.initials: K
authors.lastname: Schiffman
authors.forename: Katherine
authors.initials: K
authors.lastname: Guthrie
authors.forename: Lupe G
authors.initials: LG
authors.lastname: Salazar
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
authors.forename: Vivian
authors.initials: V
authors.lastname: Goodell
authors.forename: Corazon
authors.initials: C
authors.lastname: dela Rosa
authors.forename: Martin A
authors.initials: MA
authors.lastname: Cheever
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases