Detection of humoral response in patients with glioblastoma receiving EGFRvIII-KLH vaccines.
The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in glioblastoma multiforme (GBM) and other neoplasms. As such it represents a truly tumor-specific target for antitumor immunotherapy. Although endogenous humoral responses to EGFRvIII have been reported in patients with EGFRvIII-expressing breast cancer, it is not known whether de novo responses can be generated or endogenous responses enhanced with an EGFRvIII-specific vaccine. To assess this in clinical trials, we have developed and validated an immunoassay to measure and isolate anti-EGFRvIII and anti-KLH antibodies from the serum of patients vaccinated with an EGFRvIII-specific peptide (PEPvIII) conjugated to keyhole limpet hemocyanin (KLH). Using magnetic beads with immobilized antigen we captured and detected anti-EGFRvIII and anti-KLH antibodies in serum from patients before and after vaccinations. Using this assay, we found that significant levels of antibody for tumor-specific antigen EGFRvIII (>4 microg/mL) and KLH could be induced after vaccination with PEPvIII-KLH.
Schmittling
Robert J
RJ
Division of Neurosurgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. schmi028@mc.duke.edu
Archer
Gary E
GE
Mitchell
Duane A
DA
Heimberger
Amy
A
Pegram
Charles
C
Herndon
James E
JE
Friedman
Henry S
HS
Bigner
Darell D
DD
Sampson
John H
JH
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000097:blood* / Q000276:immunology / Q000628:therapy; D006433:Hemocyanins / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000276:immunology / Q000627:therapeutic use*; D014611:Vaccination / Q000379:methods
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D006433:Hemocyanins; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; C032808:keyhole-limpet hemocyanin