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.
['Kobayashi|Yukio|Y|', 'Sakura|Toru|T|', 'Miyawaki|Shuichi|S|', 'Toga|Kazuyuki|K|', 'Sogo|Shinji|S|', 'Heike|Yuji|Y|']
D000368:Aged D000369:Aged, 80 and over D019496:Cancer Vaccines D045744:Cell Line, Tumor D015331:Cohort Studies D004305:Dose-Response Relationship, Drug D005260:Female D015789:HLA-A2 Antigen D059806:HLA-DR beta-Chains D006801:Humans D015470:Leukemia, Myeloid, Acute D008213:Lymphocyte Activation D008297:Male D020714:Maximum Tolerated Dose D008875:Middle Aged D012074:Remission Induction D013602:T-Lymphocytes, Cytotoxic D018417:Th1 Cells D022223:Vaccines, Subunit D025721:WT1 Proteins
OCV-501 Acute myeloid leukemia WT1 Immunotherapy Helper peptide Cancer vaccine