2001 Fiscal Year Final Research Report Summary
Identification of human tumor antigens and immunotherapy
| Project/Area Number |
11694301
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SATO Noriyuki Sapporo Medical University School of Medicine, Professor, 医学部, 教授 (50158937)
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| Project Period (FY) |
1999 – 2001
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| Keywords | tumor vaccine / CTL / immunotherapy / HLA-A24 / antigenic peptide / hsc73 / molecular chaperone / ER translocation |
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| Research Abstract |
Our studies indicated that 1) inhibitors of apoptosis (IAP) protein were expressed preferentially in neoplastic cells but not in normal tissues. Such IAP, particulary, survivin-and livin-derived HLA-A24-restricted peptides could be immunogenic to cancer patients. 2) Recoverin protein that normally expresses in retina was also detected in more than 50 % of cancer cells and cancer tissues. Recoverin-derived HLA-A24-restricted peptide could also specifically induce CTL in the cancer patients of various tissue origins. 3) SYT-SSX chromosomal translocation (X;18) fusion protein was expressed specifically in approximately 95 % of synovial sarcomas. This protein-derived HLA-A24-restricted peptide could induce antigen-specific CTL, and tetramer study suggested that the precursor of these CTL was detected more frequently in patients with lung metastasis of this tumor. These data implied that above peptides may be useful in human cancer immunotherapy.
We also assessed the role of molecular chaperone, hsc73, in the transport of antigenic peptide into the ER. The data indicated that N-terminus-extended peptides that showed high, but not low, affinity to hsc73 could enter into the ER. This observation is important in determining tumor vaccines, because hsc73-binding peptides may be preferentially associated with MHC class I molecules.
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[Publications] Maeda, A., Ohguro, H., Nabeta, Y., Kuroki, Y., Sato, N.et al.: "Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, cancer associated retinopathy antige, to achieve a clinical better prognosis in a paraneoplastic syndrome"Eur. J. Immunol.. 31. 563-572 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Rong, S., Ikeda, H., Sato, Y., Hirohashi, Y., Tamura, Y., Sahara, H., Sato, T., Maeda, A., Ohguro, H., Sato, N.: "Frequent detection of anti-recoverin cytotoxic T-lymphocytes precursor in peripheral blood of cancer patients by using an HLA-A24-recoverin-tetramer"Cancer Immunol. Immunother.. (in press).
Description
「研究成果報告書概要(和文)」より
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[Publications] Shigehara, K., Shujubo, N., Ohmichi, M., Takahashi, R., Kon, S., Okamura, H., Kurimoto, M., Hiraga, Y., Tatsuno, T., Abe, S. and Sato, N.: "IL-12 and IL-18 are increased and stimulate IFN-g production in sarcold lungs"J. Immunol.. 166. 642-649 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Kishi, A., Ichinohe, T., Hirai, I., Kamiguchi, K., Tamura, Y., Kinebuchi, M., Torigoe, T., Ichimiya, S., Kondo, N., Ishitani, K., Yoshikawa, T., Kondo, M., Matsuura, A. and Sato, N.: "The cell surface-expressed HSC70-like molecule preferentially reacts with rat T cell receptor d6 family"Immunogenetics. 53. 401-409 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Maeda, A., Ohguro, H., Nabeta, Y., Hirohashi, Y., Sahara, H., Maeda, T., Wada, Y., Sato, T., Chuns, Y., Nishimura, Y., Kuroki, Y., and Sato, N.: "Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, cancer associated retinopathy antige, to achieve a clinical better prognosis in a pananeoplastic syndrome"Eur. J. Immunol.. 31. 563-572 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sahara, H., Nabeta, Y., Torigoe, T., Hirohashi, Y., Ichimiya, S., Wada, Y., Takehashi, N., Jimbow, K., Yajima, T., Watanabe, N., Kikuchi, K., and Sato, N.: "A gene encoding human gastric signete ring cell carcinoma antigen recognized by HLA-A31-restricted cytotoxic T lymphocytes"J. Immunother. (in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Rong, S., Ikeda, H., Sato, Y., Hirohashi, Y., Tamura, Y., Sahara, H., Sato, T., Maeda, A., Ohguro, H., and Sato, N.: "Frequent detection of anti-recoverin cytotoxic T-lymphocytes precursor in peripheral blood of cancer patients by using an HLA-A24-recoverin-tetramer"Cancer Immunol. Immunother.. (in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sato, Y., Nabeta, Y., Tsukahara, T., Hirohashi, Y., Rone. S., Maeda, A., Sajara, H., Ikeda, H., Torigoe, T., Ichimiya, S., Wada, T., Yamashita, T., Hiraga, R, Kawai, A., Ishii, T., Araki, N., Kmyoui, A., Matsumoto, S., Umeda, T., Ishii, S., Kawaguchi, S. and Sato, N.: "Detection and induction of cytotoxic T lymphocytes Specific for SYT-SSX-derived peptides in HLA.-A24+ patients with synovial sarcoma"J. Immunol.. (in press).
Description
「研究成果報告書概要(欧文)」より
