1995 Fiscal Year Final Research Report Summary
In vivo experimeted model for anticancer therapy using murine and humanized monoclonal antibodies
| Project/Area Number |
06680838
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | Tokai University School of Medicine |
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Principal Investigator |
SHIMAMURA Kazuo Tokai University, School of Medicine, Accistant Pro., 医学部, 講師 (00119679)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUDA Yutaka Tokai University, School of Medicine, Accistant Pro., 医学部, 講師 (20163975)
TAMAOKI Norikazu Tokai University, School of Medicine, Pro., 医学部, 教授 (50055860)
UEYAMA Yoshito Tokai University, School of Medicine, Assciate Pro., 医学部, 助教授 (30072408)
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| Project Period (FY) |
1994 – 1995
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| Keywords | c-erbB-2 / SCID mice / anti-tumor effect / humanized monoclonal antibody |
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| Research Abstract |
The c-erbB-2 product is thought to be an unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo antitumor effects of a humanized antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2 overexpressing SK-BR-3 cell line. In vivo treatment of SCID mice carrying the c-erbB-2 overexpressing 4-1ST human gastric carcinoma xanograft anti-tumor activity. Furthemore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was signnificantly augmented with rhu4D5, but not with mu4D5.
These results indicate that rhu4D5 might be better in patients than predicted from preclinical studies.
Injection of 4-1ST cells into the tail vein resulted in death of the mice within 80 days. Threatment of animals with rhu4D5 prolonged murine survival time slightly but not the level with mu4D5.
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