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

Authors: Maslak, P. G.; Dao, T.; Krug, L. M.; Chanel, S.; Korontsvit, T.; Zakhaleva, V.; Zhang, R.; Wolchok, J. D.; Yuan, J.; Pinilla-Ibarz, J.; Berman, E.; Weiss, M.; Jurcic, J.; Frattini, M. G.; Scheinberg, D. A.
Article Title: Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia
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 4WT1 peptides (200 μg each) plus immune adjuvants over 12 weeks. Immune responses were evaluated by delayed-type hypersensitivity, CD4+ T-cell proliferation, CD3+ T-cell interferon-γ 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-γ-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 poly valent 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. This study was registered at as #NCT00398138. © 2010 by The American Society of Hematology.
Keywords: adult; clinical article; treatment response; aged; disease-free survival; middle aged; young adult; unclassified drug; oncoprotein; acute granulocytic leukemia; genetics; leukemia, myeloid, acute; clinical trial; drug activity; mortality; cancer combination chemotherapy; drug safety; treatment duration; disease free survival; cytarabine; follow up; methodology; cd8+ t lymphocyte; cell proliferation; cd8-positive t-lymphocytes; edema; reverse transcription polymerase chain reaction; pain; granulocyte macrophage colony stimulating factor; genetic transcription; cytotoxicity; kaplan-meiers estimate; biosynthesis; immunology; immune response; gamma interferon; cancer vaccine; cancer vaccines; reverse transcriptase polymerase chain reaction; pilot study; pilot projects; immunogenicity; oncogene proteins; montanide isa 51; cd4+ t lymphocyte; cd4-positive t-lymphocytes; vaccination; daunorubicin; erythema; remission; remission induction; cytotoxicity, immunologic; idarubicin; interferon-gamma; kaplan meier method; wt1 protein; peptide vaccine; hla a0201 antigen; cd3+ t lymphocyte; hla a antigen; hla-a antigens; recombinant granulocyte macrophage colony stimulating factor; hypersensitivity reaction; vaccines, subunit; urticaria; cell secretion; subunit vaccine; delayed hypersensitivity; wt1 proteins; hypersensitivity, delayed; injection site pruritus; injection site swelling; polyvalent wilms tumor gene 1 peptide vaccine; hla-a0201 antigen; injection site irritation; injection site redness; injection site tenderness; larynx spasm
Journal Title: Blood
Volume: 116
Issue: 2
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2010-07-15
Start Page: 171
End Page: 179
Language: English
DOI: 10.1182/blood-2009-10-250993
PUBMED: 20400682
PROVIDER: scopus
PMCID: PMC2910606
Notes: --- - "Cited By (since 1996): 6" - "Export Date: 20 April 2011" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Lee M Krug
    202 Krug
  2. Jedd D Wolchok
    608 Wolchok
  3. Joseph G Jurcic
    123 Jurcic
  4. Suzanne M Chanel
    28 Chanel
  5. Tao Dao
    57 Dao
  6. Peter Maslak
    161 Maslak
  7. Jianda Yuan
    92 Yuan
  8. Mark Weiss
    80 Weiss
  9. Ellin Berman
    89 Berman
  10. Rong Hua Zhang
    17 Zhang