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 www.clinicaltrials.gov 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
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77955481538&partnerID=40&md5=e73cb2be690f127c70bec1e1a8e7ec0e
Notes:	--- - "Cited By (since 1996): 6" - "Export Date: 20 April 2011" - "CODEN: BLOOA" - "Source: Scopus"

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