1999 Fiscal Year Final Research Report Summary
Cancer vaccine with hydrophobized polysaccharide oncoprotein complex
| Project/Area Number |
09557046
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | Mie University |
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Principal Investigator |
SHIKU Hiroshi Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80154194)
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| Co-Investigator(Kenkyū-buntansha) |
SUNAMOTO Junzo Kyoto University, Professor, 大学院, 教授 (80037811)
NAKAMURA Hideo Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., Investigator, 横浜研究所, 主任研究員
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| Project Period (FY) |
1997 – 1999
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| Keywords | hydrophobized polysaccharide / pullulan / CTL / tumor antigen / HER2 / adjuvant / tumor rejection antigen / antigen peptide |
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| Research Abstract |
We designed a novel and simple protein delivery system for center immunotherapy : cholesteryl group-bearing polysaccharides, mannan and pullulan (CHM and CHP), complexed with the truncated HER2 protein containing the 147N-terminal amino acids. CHM-HER2 were able to induce CD8ィイD1+ィエD1 CTLs against HER2ィイD1+ィエD1 tumors. These CTLs were KィイD1dィエD1 restricted and recognized specifically HER2p63-71, a part of a truncated HER2 protein used as an immunogen. Mice immunized with CHM-HER2 or CHP-HER2 before tumor challenge, successfully rejected HER2ィイD1+ィエD1 tumors. The complete rejection of tumors implantation. In the effector phase of in vino tumor rejection, CDィイD1+ィエD1 T cells played a major role.
Mice were immunized with CHP-HER2 and proliferative response of CD8ィイD1+ィエD1 T cells was examined by stimulating them with DCs pretreated with CHP-HER2, which shows that DCs can incorporate CHP-HER2 efficiently and present cognate peptides to CD8ィイD1+ィエD1 T cells after appropriate processing. We further examined whether DCs treated ex vivo with CHP-HER2 could be used as vaccine against HER2 expressing tumor cells. HER2 expressing tumor cells were inoculated into mice, and 10 days later, vaccinated with CHP-HER2 pretreated with CHP-HER2 was started. Only in the group of mice vaccinated with CHP-HER2 pretreated DCs, complete eradication of tumor was observed. Human bone marrow-derived dendritic cells cocultured with CHP-HER2 became susceptible to a HLA-A24 restricted CTL clone specific for HER2p63-71 and also induced its proliferation.
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[Publications] Ikeda, H., Ohta, N., Furukawa, K., Miyazaki, H., Wang, L., Furukawa. K., Kuribayashi, K., Old, L.J. and Shiku, H.: "Mutated MAP kinase ; A tumor rejection antigen of mouse sarcoma"Proc. Natl. Acad. Sci. USA. 94. 6375-6379 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Nagata, Y., Furugen, R., Hiasa, A., Ikeda, H., Ohta, N., Furukawa, K., Nakamura, H., Furukawa, K., Kanematsu, T. and Shiku, H.: "Peptides derived from a wild type murine proto-oncogene ceerB-2/HER2/neu can induce CTL and tumor suppression in syngeneic hosts."J. Immunol. 159. 1336-1343 (1997)
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[Publications] Schmitt, M., Ikeda, H., Nagata, Y., Gu, X., Wang, L., Kuribayashi, K. and Shiku, H.: "Involvement of T cell subsets and natural killer (NK) cells in the growth suppression of murine fibrosarcoma cells transfected with interleukin-12 (IL-12) genes"Int. J. Cancer. 72. 505-511 (1997)
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[Publications] Miwa, H., Mizutani, M., Mahmud, N., Yamaguchi, M., Takahashi, T., Shikami, M., Shiku H., Tanaka, I., Nakase, K., Nasu, K., Dohy, H., Ueda, T., Kamada, N and Kita, K.: "Biphasic expression of CD4 in acute myelocytic leukemia (AML) cells : AML of monocyte origin and hematopoietic precursor cell origin"Leukemia. 12. 44-51 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Gu, X-G., Schmitt M., Hiasa, A., Nagata, Y., Ikeda, H., Sasaki., Y., Akiyoshi, K., Sunamoto, J., Nakamura, H., Kuribayashi, K. and Shiku H.: "A novel hydorophobized polysaccharide/oncoprotein complex vaccine induces in vitro and in vivo cellular and humoral immune responses against HER2 expressing murine sarcomas"Cancer Res.. 58. 3385-3390 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Wang L., Ikeda, H., Ikuta, Y., Schmitt M., Miyahara Y., Takahashi Y., Gu X., Nagata Y., Sasaki Y., Akiyoshi K., Sunamoto J., Nakamura H., Kurabayashi K., and Shiku H.: "Bone marrow-derived dendritic cells incorporate and process hydrophobized polysaccharide/oncoprotein complex as antigen presenting cells"Int J. Oncol. 14. 695-701 (1999)
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