Development of novel immuno-gene therapy for gastrointestinal cancer using antigen presenting function of heat shock protein
| Project/Area Number |
10671132
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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 |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
KITAGAWA Yuko Keio University School of Medicine, Department of Surgery, Assistant Professor, 医学部, 助手 (20204878)
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| Co-Investigator(Kenkyū-buntansha) |
TODA Masahiro Keio University School of Medicine, Institute for Advanced Medical Research Assistant Professor, 医学部, 助手 (20217508)
KAWAKAMI Yutaka Keio University School of Medicine, Institute for Advanced Medical Research Professor, 医学部, 教授 (50161287)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | heat shock protein / gastrointestinal cancer / immuno-gene therapy / tumor rejection / antigen presentation / dendritic cell |
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| Research Abstract |
The anti-tumor effect of heat-shock proteins (hsp) derived from CMS7-ME tumor was investigated. CMS7-ME, cell line was established by a HER2/neu transduction into the CMS7 derived from BALB/c mice fibrosarcoma. Three kinds of hsps, gp-96, hsp-70, hsp-90 were extracted from CMS7-ME and subcutaneously inoculated into the other mice. CMS7-ME tumor was implanted into these hsp-immunized mice. In gp96 or hsp-70 treated group, growth inhibitory effect implanted of CMS7-ME was observed. There is no anti-tumor effect in hsp-90 treated group.
In the model of CT-26, N-nitroso-N-methylurethane induced BALB/c colonic tumor, an anti-tumor effect of CT-26 derived hsps was investigated, gp-96 derived from CT-26 showed growth inhibitory effect to CT-26 tumor. There is no growth inhibitory effect of CT-26 derived hsp-70 or hsp-90 treated groups. The complex of gp96 extracted from normal liver and CT-26 specific peptide, AH-1 showed anti-tumor effect in this model. However an induction of AH-1 specific cytotoxic T cells was not detected in this experiment.
Anti-tumor effect of dendritic cells (DC) pulsed with gp96 derived from CT-26 was compared with that of DC pulsed with AH-1. DC pulsed with gp96 derived from CT-26 showed more significant growth inhibitory effect to CT-26 tumor in comparison with AH-1 pulsed DC.
These results suggest that the role of tumor derived hsp in the antigen presenting process.
Further investigation would be required to confirm the mechanisms of these effects as a pre-clinical investigation.
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Report
(3 results)
Research Products
(14 results)
