| Project/Area Number |
15390392
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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 | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | University of Yamanashi |
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Principal Investigator |
KONO Koji University of Yamanashi, Department of Research Interdisciplinary graduate school of medicine and engineering, Associate Professor, 大学院・医学工学総合研究部, 助教授 (40283204)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAI Hidemitsu University of Yamanashi, University of Yamanashi Hospital, Research Associate, 医学部附属病院, 助手 (10345712)
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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 |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | Cancer vaccination / Antibody therapy / gastric cancer / esophageal cancer / HER-2 / 食道がん / 胃癌 / Herceptin |
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| Research Abstract |
With the present research glant, we found that Herceptin enhances class I-restricted antigen presentation recognized by HER-2-specific CTLs, resulting in the enhancement of HER-2 specific CTL activity against HER-2 overexpressing tumor cells. These observations prompted us to investigate the synergistic effect of combination therapy of HER-2-vaccination with Herceptin. On the other hand, we showed that HER-2 overexression was observed in 23% of gastric caner and 35% of esophageal cancers. Then, we initiated a phase-1 clinical trial in gastric and esophageal cancer patients using HER-2-vaccination combined with Herceptin. Six enrolled patients, who had HER-2 overexpressing tumors and were HLA-A2 or HLA-A24 positive, received four vaccinations and administration of Herceptin. Two of the patients showed a partial clinical response, stable disease in one patient and progressive disease in 3 patients. HER-2-epitope-specific recognition could be enhanced in 6 of 6 patients after the combination therapy evaluated by Elispot and tetramer assay. These observations strongly indicated that the combination therapy of the vaccination with Herceptin could induce the synergistic effect in anti-HER-2 immune response in comparison with vaccination alone.
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