2003 Fiscal Year Final Research Report Summary
Development of cancer immunotherapy targeting WT1 which highly expresses in patients with hematopoictic maliganacies including leukemia.
| Project/Area Number |
14570976
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
OKA Yoshihiro Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20273691)
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| Project Period (FY) |
2002 – 2003
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| Keywords | WT1 / leukemia / cancer immunotherapy / cancer vaccine |
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| Research Abstract |
IgM-and IgG-type WT1 antibodies were detected in patients with heniatopoietic malignancies including MDSand leukemia, indicating that WT1 protein is highly immunogenic and not only humoral but also cellular WT1-specific immune responses which induced immunoglobulin class-switch of WT1 antibodies were spontaneously elicited in the patients. These findings provided us with a rationale for WT1 protein-directed immunotherapy for leukemia.
A novel 9 mer WT1 peptide (modified WT235), in which one amino acid residue at an anchor position was replaced by another amino acid, was shown to exert very strong cytotoxicity against leukemia cells. This peptide may be very useful for cancer immunotherapy in clinical settings.
In lck promotor-driven WT1-transgenic (Tg) mice, the differentiation of T-lineage cells in thymus was shown to be blocked. This result directly indicated that WT1 is involved in the differentiation of T-lineage lymphocytes. Differentiation inhibition of cells may lead to growth promotion of the cells, namely, leukemogenesis. Careful observation of the Tg-mice is ongoing.
We established a mouse "therapeutic model" for WT1 peptide cancer vaccine, in which mice vaccinated with WT1 peptide in combination with BCG-CWS efficiently rejected WT1-expressing leukemia cells which had been transplanted before vaccination.
We staffed Phase I clinical trial of WT1 peptide cancer vaccine for MDS or leukemia. We obtained some cases in which leukemic blast cells and/or WT1 level decreased after the vaccination, indicating that the vaccine might be useflil for the treatment of hematopoietic malignancies.
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