1995 Fiscal Year Final Research Report Summary
ANTI-TUMOR IMMUNOTHERAPY WITH A HUMANIZED MONOCLONAL ANTIBODY AGAINST HUMAN PROTO-ONCOGENE PRODUCT
| Project/Area Number |
06671229
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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 |
General surgery
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| Research Institution | TOKAI UNIVERSITY |
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Principal Investigator |
TOKUDA Yutaka TOKAI UNIV.SCHOOL OF MED., ASSISTANT PROFESSOR, 医学部, 講師 (20163975)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMAMURA Kazuo TOKAI UNIV.SCHOOL OF MED., ASSOCIATE PROFESSOR, 医学部, 講師 (00119679)
UEYAMA Yoshito TOKAIUNIV.SCHOOL OF MED., ASSOCIATE PROFESSOR, 医学部, 助教授 (30072408)
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| Project Period (FY) |
1994 – 1995
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| Keywords | C-erbB-2 / Proto-oncogene / Humanized monoclonal antibody / Anti-tumor effect / SCID mice |
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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 anti-tumor 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 xenograft with rhu4D5 revealed that the recombinant protein had potent anti-tumor activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5.
These results indicate that rhu4D5 mmight be better in patients than predicted from preclinical studies. A clinical trial would be warranted.
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