Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide

Int J Cancer. 2016 Sep 15;139(6):1391-401. doi: 10.1002/ijc.30182. Epub 2016 May 31.

Abstract

We previously evaluated Wilms' tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1-235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1-235 IgG antibody subclass was Th1-type, IgG1 and IgG3 . WT1-235 IgG antibody production was significantly and positively correlated with both progression-free survival (PFS) and overall survival (OS). Importantly, the combination of WT1-235 IgG antibody production and positive delayed type-hypersensitivity (DTH) to the WT1-235 peptide was a better prognostic marker for long-term OS than either parameter alone. These results suggested that WT1-235 peptide vaccination induces not only WT1-235-specific CTLs as previously described but also WT1-235-specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine-treated patients.

Keywords: WT1 IgG antibody; WT1 peptide-based immunotherapy; glioblastoma; predictive marker.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glioblastoma / immunology*
  • Glioblastoma / mortality*
  • Glioblastoma / therapy
  • HLA-A24 Antigen / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Immunotherapy
  • Male
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / immunology*
  • Prognosis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Treatment Outcome
  • Vaccination
  • WT1 Proteins / chemistry
  • WT1 Proteins / immunology*
  • Young Adult

Substances

  • Biomarkers
  • Cancer Vaccines
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • Immunoglobulin G
  • Peptides
  • WT1 Proteins