Humoral epitope-spreading following immunization with a HER-2/neu peptide based vaccine in cancer patients.
HER-2/neu is a tumor antigen in patients with breast and ovarian cancer. Multiple varieties of vaccine strategies are being developed to immunize patients against HER-2/neu. Studies in animal models have demonstrated both T cell and antibody immunity are needed to mediate an antitumor response. Thirty-five patients, immunized with HER-2/neu peptide based vaccines, were evaluated for the generation of HER-2/neu-specific antibody immunity. Sixty percent of patients developed HER-2/neu IgG specific antibody responses to at least one peptide included in their vaccine. Twenty-nine percent of patients developed IgG immunity to the native HER-2/neu protein after peptide immunization. Humoral intramolecular epitope-spreading within the HER-2/neu protein occurred in 49% of immunized patients. Intermolecular epitope-spreading to p53 was evident in 20% of vaccinated patients. Of those patients who developed new immunity to p53, 71% had demonstrated antibody epitope-spreading within HER-2/neu.
Disis
Mary L
ML
Tumor Vaccine Group, Division of Oncology, University of Washington, Seattle, Washington 98195-6527, USA. ndisis@u.washington.edu
Goodell
Vivian
V
Schiffman
Kathy
K
Knutson
Keith L
KL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology; D014612:Vaccines / Q000276:immunology* / Q000627:therapeutic use
D000906:Antibodies; D000939:Epitopes; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D014612:Vaccines