| RRC ID |
65544
|
| 著者 |
Kobayashi Y, Sakura T, Miyawaki S, Toga K, Sogo S, Heike Y.
|
| タイトル |
A new peptide vaccine OCV-501: in vitro pharmacology and phase 1 study in patients with acute myeloid leukemia.
|
| ジャーナル |
Cancer Immunol Immunother
|
| Abstract |
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.
|
| 巻・号 |
66(7)
|
| ページ |
851-863
|
| 公開日 |
2017-7-1
|
| DOI |
10.1007/s00262-017-1981-3
|
| PII |
10.1007/s00262-017-1981-3
|
| PMID |
28321480
|
| PMC |
PMC5489634
|
| MeSH |
Aged
Aged, 80 and over
Cancer Vaccines / administration & dosage*
Cancer Vaccines / immunology
Cancer Vaccines / pharmacology
Cell Line, Tumor
Cohort Studies
Dose-Response Relationship, Drug
Female
HLA-A2 Antigen / genetics
HLA-DR beta-Chains / genetics
Humans
Leukemia, Myeloid, Acute / therapy*
Lymphocyte Activation / drug effects
Male
Maximum Tolerated Dose
Middle Aged
Remission Induction
T-Lymphocytes, Cytotoxic / drug effects
T-Lymphocytes, Cytotoxic / immunology
Th1 Cells / drug effects
Th1 Cells / immunology
Vaccines, Subunit / administration & dosage
Vaccines, Subunit / immunology
Vaccines, Subunit / pharmacology
WT1 Proteins / administration & dosage*
WT1 Proteins / immunology
WT1 Proteins / pharmacology
|
| IF |
5.442
|
| リソース情報 |
| ヒト・動物細胞 |
B-lymphoblastoid cell lines |
