2002 Fiscal Year Final Research Report Summary
Identification of novel cancer-specific antigens and application for cellular imunotherapy of hematological malignancies
| Project/Area Number |
13470206
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Ehime University |
|---|
Principal Investigator |
YASUKAWA Masaki Ehime University Faculty of Medicine, Associate Professor, 医学部, 助教授 (60127917)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAKUSHIJIN Yoshihiro Ehime University Faculty of Medicine, Instructor, 医学部, 助手 (30294797)
ABE Yasuhito Ehime University Faculty of Medicine, Associate Professor, 医学部, 助教授 (30184229)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | Cancer antigens / Immunotherapy / Leukemia / Cytotoxic T lymphocytes / HLA / WT1 / Telomerase |
|---|
| Research Abstract |
To identify the novel cancer-associated antigens and to develop the novel immunotherapy for hematological malignancies, this study was performed. The data obtained from the series of experiments are as follows.
1) A WT1-specific, HLA-A24-restricted CTL clone (designated TAK-1) exhibited cytotoxicity against lung cancer cell lines bearing HLA-A24 but did not lyse cells lacking this HLA. Adoptive transfer of TAK-1 into nude mice that had been engrafted with an HLA-A24-positive lung cancer cell line resulted in inhibition of the cancer cell growth and prolonged survival. These findings strongly suggest that WT1 is a universal tumor-associated antigen and that WT1 -targeting immunotherapy offers a potentially effective treatment option for lung cancer as well as leukemia.
2) A novel WT1-derived peptide-specific CD8^+ CTL line, designated NIM-1 was established. NIM-1 lysed HLA-A24-positive leukaemia cells, but not HLA-A24 negative leukaemia cells or normal cells.
3) Immature dendritic cells (D
… More
Cs) were loaded with leukemia cells with t(6 ; 9) or t(9 ; 22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4^+ T-lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4^+ T-lymphocyte clones produced interferon-γ(IFN-γ) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6 ; 9) and t(9 ; 22), respectively. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4^+ T lymphocytes.
4) In order to clarify the roles of perforin in antigen-specific cytotoxicity mediated by human CD4^+ CTLs, antigen-specific human CD4^+ T-lymphocyte clones were established from a patient with hereditary perforin deficiency and their cytotoxic activities were investigated. The data demonstrated that perforin-negative CD4^+ CTLs can exert cytotoxicity against Fas-sensitive target cells ; however, perforin plays essential roles in antigen-specific cytotoxicity mediated by human CD4^+ as well as CD8^+ CTLs. Less
|
Research Products
(12 results)
-
-
-
-
-
-
-
[Publications] Hamada, M., Yakushijin, Y., Watanabe, I., Kakimoto, M., Yasukawa, M. and Fujita, S.: "Aurora2/BTAK/STK15 is involved in cell-cycle checkpoint and cell survival of aggressive non-Hodgkin's lymphoma"Br.J.Haematol.. (in press).
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yanai, F., Ishii, E., Kojima, K., Hasegawa, A., Azuma, T., Hirose, S., Suga, N., Mitsudome, A., Zaitsu, M., Ishida, Y., Shirakata, Y., Sayama, K., Hashimoto, K. and Yasukawa, M.: "Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4^+ T lymphocytes ; analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells"J.Immunol.. 170. 2205-2213 (2003)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Makita, M., Azuma, T., Hamaguchi, H., Niiya, H., Kojima, K., Fujita, S., Tanimoto, M., Harada, M. and Yasukawa, M.: "Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4^+ T lymphocytes"Leukemia. 16. 2400-2407 (2002)
Description
「研究成果報告書概要(欧文)」より
-
-
[Publications] Makita, M., Hiraki, A., Azuma, T., Tsuboi, A., Oka, Y., Sugiyama, H., Fujita, S., Tanimoto, M., Harada, M. and Yasukawa, M.: "Antilung cancer effect of WT1-specific cytotoxic T lymphocytes"Clin.Cancer Res.. 8. 2626-2631 (2002)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Azuma, T., Makita, M., Ninomiya, K., Fujita, S., Harada, M. and Yasukawa, M.: "Identification of a novel WT1-derived peptide which induces human leucocyte antigen-A24-restricted anti-leukaemia cytotoxic T lymphocytes"Br.J.Haematol.. 116. 601-603 (2002)
Description
「研究成果報告書概要(欧文)」より
