Phase I trial of Wilms' Tumor 1 (WT1) peptide vaccine with GM-CSF or CpG in patients with solid malignancy

Anticancer Res. 2012 Jun;32(6):2263-9.

Abstract

Background: The aim of this study was to investigate the safety and efficacy of combinatorial use of granulocyte-macrophage colony-stimulating factor (GM-CSF) and CpG oligodeoxynucleotides (CpG-ODN) as immunoenhancement adjuvants in Wilms' Tumor 1 (WT1) vaccine therapy for patients with solid malignancy.

Patients and methods: The patients were placed into treatment groups as follows: WT1 peptide alone, WT1 peptide with GM-CSF (100 μg) and WT1 peptide with CpG-ODN (100 μg). HLA-A *2402 or *0201/*0206-restricted, WT1 peptide emulsified with Montanide ISA51 was injected intradermally every week for eight weeks. Toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 3.0. Tumor size, which was measured by computed tomography, was determined every four weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors.

Results: The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The disease control rate of the groups treated with WT1 peptide alone (n=10), with combinatorial use of GM-CSF (n=8) and with combinatorial use of CpG-ODN (n=10), in the initial two months was 20%, 25% and 60%, respectively.

Conclusion: Addition of GM-CSF or CpG-ODN to the WT1 peptide vaccine for patients with solid malignancy was safe and improved the effectiveness of clinical response.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / adverse effects
  • Aged
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • CpG Islands* / immunology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Immunohistochemistry
  • Male
  • Mannitol / administration & dosage
  • Mannitol / adverse effects
  • Mannitol / analogs & derivatives
  • Mannitol / immunology
  • Middle Aged
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Oleic Acids / administration & dosage
  • Oleic Acids / adverse effects
  • Oleic Acids / immunology
  • Oligonucleotides / administration & dosage*
  • Oligonucleotides / adverse effects
  • Oligonucleotides / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology
  • WT1 Proteins / administration & dosage*
  • WT1 Proteins / adverse effects
  • WT1 Proteins / immunology

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Oleic Acids
  • Oligonucleotides
  • Vaccines, Subunit
  • WT1 Proteins
  • montanide ISA 51
  • Mannitol
  • Granulocyte-Macrophage Colony-Stimulating Factor