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 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.
authors.affiliation: Leukemia Service, Department of Medicine, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. maslakp@mskcc.org
authors.forename: Peter G
authors.initials: PG
authors.lastname: Maslak
authors.forename: Tao
authors.initials: T
authors.lastname: Dao
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chanel
authors.forename: Tatyana
authors.initials: T
authors.lastname: Korontsvit
authors.forename: Victoria
authors.initials: V
authors.lastname: Zakhaleva
authors.forename: Ronghua
authors.initials: R
authors.lastname: Zhang
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.forename: Jianda
authors.initials: J
authors.lastname: Yuan
authors.forename: Javier
authors.initials: J
authors.lastname: Pinilla-Ibarz
authors.forename: Ellin
authors.initials: E
authors.lastname: Berman
authors.forename: Mark
authors.initials: M
authors.lastname: Weiss
authors.forename: Joseph
authors.initials: J
authors.lastname: Jurcic
authors.forename: Mark G
authors.initials: MG
authors.lastname: Frattini
authors.forename: David A
authors.initials: DA
authors.lastname: Scheinberg
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic; D018572:Disease-Free Survival; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D010865:Pilot Projects; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D025721:WT1 Proteins / Q000276:immunology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015513:Oncogene Proteins; D022223:Vaccines, Subunit; D025721:WT1 Proteins; D007371:Interferon-gamma
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