Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia

Blood. 2010 Jul 15;116(2):171-9. doi: 10.1182/blood-2009-10-250993. Epub 2010 Apr 16.

Abstract

A pilot study was undertaken to assess the safety, activity, and immunogenicity of a polyvalent Wilms tumor gene 1 (WT1) peptide vaccine in patients with acute myeloid leukemia in complete remission but with molecular evidence of WT1 transcript. Patients received 6 vaccinations with 4 WT1 peptides (200 microg each) plus immune adjuvants over 12 weeks. Immune responses were evaluated by delayed-type hypersensitivity, CD4+ T-cell proliferation, CD3+ T-cell interferon-gamma release, and WT1 peptide tetramer staining. Of the 9 evaluable patients, 7 completed 6 vaccinations and WT1-specific T-cell responses were noted in 7 of 8 patients. Three patients who were HLA-A0201-positive showed significant increase in interferon-gamma-secreting cells and frequency of WT1 tetramer-positive CD8+ T cells. Three patients developed a delayed hypersensitivity reaction after vaccination. Definite related toxicities were minimal. With a mean follow-up of 30 plus or minus 8 months after diagnosis, median disease-free survival has not been reached. These preliminary data suggest that this polyvalent WT1 peptide vaccine can be administered safely to patients with a resulting immune response. Further studies are needed to establish the role of vaccination as viable postremission therapy for acute myeloid leukemia.

Trial registration: ClinicalTrials.gov NCT00398138.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cytotoxicity, Immunologic
  • Disease-Free Survival
  • Female
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Oncogene Proteins / genetics
  • Oncogene Proteins / immunology
  • Oncogene Proteins / therapeutic use*
  • Pilot Projects
  • Remission Induction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vaccination / methods*
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • WT1 Proteins / immunology
  • WT1 Proteins / therapeutic use*
  • Young Adult

Substances

  • Cancer Vaccines
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Oncogene Proteins
  • Vaccines, Subunit
  • WT1 Proteins
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT00398138