| Project/Area Number |
15590665
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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 |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
OKAMOTO Tetsuro Sapporo Medical University, School of Medicine, the 4^<th> Department of Internal Medicine, Instructor, 医学部, 助手 (60332912)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | DNA vaccine / Calreticulin / CEA / immunotherapy |
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| Research Abstract |
Carcinoembryonic antigen (CEA) has been identified as an attractive target for active vaccination approaches against gastrointestinal. Several clinical studies using DNA vaccine encoding CEA have been assessed. However its safety and immumogenicity have been established, clinical response stayed in only their stabilization of diseases. Expecting more effective immune responses, clinical trials were planned to combine with several adjuvants or cytokines, but they did not show additional responses. Calreticulin (CRT) can enhance antigen specific T cell mediated immune responses and have antiangiogenic effect by the function of its Ca2+binding protein. Therefore we engineered an innovative DNA vaccine, which expressing CRT chimerically liked to CEA (pcCRT/CEA) for the treatment of mice model bearing CEA expressing tumor, we also generated no insert (pcDNA3.1), CRT (pcCRT) and CEA (pcCEA) expressing plasmids. DNA vaccination was performed twice (day 0 and 7) intramuscularly and on day 21 tumor cells were inoculated subcutaneously. The tumor size on the mice immunized with pcCEA was smaller than with pcDNA3.1 or with pcCRT alone. And the group vaccinated mixed vaccine (pcCRT and pcCEA) generated smallest tumors, furthermore the mice group received pcCRT/CEA vaccination remained tumor free for 25 days after inoculation of the tumor cells. Thus DNA vaccine therapy using CRT linked to CEA holds promise for treating gastrointestinal cancers.
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