title: Comparison of different HER2/neu vaccines in adjuvant breast cancer trials: implications for dosing of peptide vaccines.
abstract: We have performed multiple adjuvant clinical trials using immunogenic peptides from the HER2/neu protein (AE37/E75/GP2) plus (GM-CSF) given intradermally to breast cancer patients. Four trials were performed with similar dose-escalation design with increasing doses of peptide (AE37/E75/GP2) and varying amounts of GM-CSF. Dose reductions (DRs) were made for significant local and/or systemic toxicity by decreasing GM-CSF for subsequent inoculations. Ex vivo and in vivo immunologic responses were used to compare groups. Of 132 patients, 39 required DR (30 for robust local reactions [DR-L]). DR patients, particularly DR-L, had greater immune responses both ex vivo and in vivo. Postvaccine delayed-type hypersensitivity in DR-L patients compared with all others was larger for E75 (p = 0.001), AE37 (p = 0.077) and GP2 (p = 0.076). All three peptide vaccines were safe and well-tolerated. These findings have led to a clinically relevant optimal vaccine dosing strategy, which may be applicable to other peptide-based cancer vaccines.
authors.affiliation: Department of Surgery, General Surgery Service, Brooke Army Medical Center, 3851 Roger Brooke Drive, Ft. Sam, Houston, TX 78234, USA.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Benavides
authors.forename: Alan K
authors.initials: AK
authors.lastname: Sears
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Gates
authors.forename: Guy T
authors.initials: GT
authors.lastname: Clifton
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Clive
authors.forename: Mark G
authors.initials: MG
authors.lastname: Carmichael
authors.forename: Jarrod P
authors.initials: JP
authors.lastname: Holmes
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: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000628:therapy*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D022223:Vaccines, Subunit; C508053:ERBB2 protein, human