Immunization of cancer patients with HER-2/neu-derived peptides demonstrating high-affinity binding to multiple class II alleles.
OBJECTIVE
The purpose of this study was to immunize patients with HER-2/neu-overexpressing cancer with a multipeptide vaccine comprised of four class II HER-2/neu peptides that had been identified as the most immunogenic in a previous clinical trial. Furthermore, we questioned whether MHC binding affinity could predict the in vivo immunogenicity of the HER-2/neu helper peptides.


METHODS
Four putative class II HER-2/neu peptides, which were found to generate detectable specific T-cell responses (stimulation index > 2) in a majority of patients in a previous study, were used to formulate a single vaccine. The multipeptide vaccine was administered intradermally with granulocyte macrophage colony-stimulating factor as an adjuvant. Ten patients with HER-2/neu overexpressing breast or lung cancer were enrolled. HER-2/neu peptide-and protein-specific T cell and antibody immune responses were measured. Competitive inhibition assays were used to analyze the class II HER-2/neu peptides for their binding affinity to 14 common HLA-DR alleles.


RESULTS
Twenty-five percent of patients developed HER-2/neu peptide-specific T-cell immunity, and 50% developed HER-2/neu peptide-specific antibody immunity. No patient developed HER-2/neu protein-specific T cell or antibody immunity. The majority of peptides exhibited high binding affinity, in vitro, to >/==" BORDER="0">3 of the 14 DR alleles analyzed.


CONCLUSIONS
The group of peptides used in this study demonstrated high binding affinity to multiple DR alleles suggesting that in vitro binding affinity may be able to predict the in vivo immunogenicity of class II peptides. However, only a minority of patients immunized with the multipeptide vaccine developed HER-2/neu peptide-specific T cell or antibody immunity, and none developed HER-2/neu protein-specific immunity.
Salazar
Lupe G
LG
Tumor Vaccine Group, Division of Oncology, University of Washington, Seattle, Washington, USA. lsalazar@u.washington.edu
Fikes
John
J
Southwood
Scott
S
Ishioka
Glenn
G
Knutson
Keith L
KL
Gooley
Theodore A
TA
Schiffman
Kathy
K
Disis
Mary L
ML
D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D018734:Genes, erbB-2 / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments