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

Yusuke Oji, Naoya Hashimoto, Akihiro Tsuboi, Yui Murakami, Miki Iwai, Naoki Kagawa, Yasuyoshi Chiba, Shuichi Izumoto, Olga Elisseeva, Ryo Ichinohasama, Junichi Sakamoto, Satoshi Morita, Hiroko Nakajima, Satoshi Takashima, Yoshiki Nakae, Jun Nakata, Manabu Kawakami, Sumiyuki Nishida, Naoki Hosen, Fumihiro FujikiSoyoko Morimoto, Mayuko Adachi, Masahiro Iwamoto, Yoshihiro Oka, Toshiki Yoshimine, Haruo Sugiyama

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1391-1401
Number of pages11
JournalInternational Journal of Cancer
Volume139
Issue number6
DOIs
Publication statusPublished - 2016 Sep 15

Keywords

  • WT1 IgG antibody
  • WT1 peptide-based immunotherapy
  • glioblastoma
  • predictive marker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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