A new peptide vaccine OCV-501: in vitro pharmacology and phase 1 study in patients with acute myeloid leukemia.
Wilms' tumor 1 (WT1) is a promising target of new immunotherapies for acute myeloid leukemia (AML) as well as for other cancers. OCV-501 is a helper peptide derived from the WT1 protein. OCV-501 induced OCV-501-specific Type 1 T-helper (Th1) responses dose-dependently and stimulated helper activity of the specific Th1 cells in peripheral blood mononuclear cells from healthy donors. OCV-501 also enhanced the increase in WT1-killer peptide-specific cytotoxic T lymphocytes. OCV-501 stimulated the OCV-501-specific Th1 clones in an HLA class-II restricted manner and formed a complex with HLA class-II protein. OCV-501-specific Th1 clones demonstrated significant OCV-501-specific cytolytic activity against OCV-501-pulsed B-lymphoblastoid cell line cells. Based on the pre-clinical results, phase 1 clinical trial was conducted. The result of this trial suggested that the subcutaneous administration of OCV-501 once weekly for 4 weeks at doses of 0.3, 1, and 3 mg in older patients with AML during complete remission was safe and well tolerated. The maximum tolerated dose was considered to be ≥3 mg. Of the nine subjects enrolled, neither relapse nor blast cells were observed during the study. Immunological responses were observed in OCV-501-specific delayed-type hypersensitivity test. This trial was registered at http://www.clinicaltrials.gov as NCT 01440920.
Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. ykkobaya@ncc.go.jp.
Yukio
Y
Kobayashi
Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Gunma, 371-0821, Japan.
Toru
T
Sakura
Division of Hematology, Tokyo Metropolitan Ohtsuka Hospital, Toshima-ku, Tokyo, 170-8476, Japan.
Shuichi
S
Miyawaki
Department of Clinical Research and Development, Headquarters of New Product Evaluation and Development, Otsuka Pharmaceutical Co., Ltd., Minato-ku, Tokyo, 108-8242, Japan.
Kazuyuki
K
Toga
Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan.
Shinji
S
Sogo
Immunotherapy and Cell Therapy Service, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.|Translational Medicine Department, Phase 1 Group, Exploratory Oncology, Research & Clinical Trial Center, National Cancer Center Hospital, 5-1-1 Teukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Yuji
Y
Heike
D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics; D059806:HLA-DR beta-Chains / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D025721:WT1 Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology
D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D059806:HLA-DR beta-Chains; D022223:Vaccines, Subunit; D025721:WT1 Proteins
Acute myeloid leukemia; Cancer vaccine; Helper peptide; Immunotherapy; OCV-501; WT1