1987 Fiscal Year Final Research Report Summary
Targetted immunotherapy with enzyme-labeled antibodies
| Project/Area Number |
60480156
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Tokai University School of Medicine |
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Principal Investigator |
NAKANE Kazuo Tokai University School of Medicine, Professor, 医学部, 教授 (60164240)
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| Co-Investigator(Kenkyū-buntansha) |
UEYAMA Yoshito Tokai University School of Medicine, Associate Professor, 医学部, 助教授 (30072408)
HABU Sonoko Tokai Universiy School of Medicine, Associate Professor, 医学部, 助教授 (30051618)
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| Project Period (FY) |
1985 – 1987
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| Keywords | Carcinoembryonic antigen / Glucose oxidase-labeled antibody / Galactose oxidase-labeled antibody |
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| Research Abstract |
Carcinoembryonic antigen (CEA) is found only at the brush border of normal colonic columnar epithelial cells,but is found all around the surface of colonic cancer cells. By taking an advantage of the change on the distribution of antigens on the surface of transformed epithelial cells, we undertook to develop a method to eliminate such neoplastic cells from the body. As a preliminary experiment, nude mice bearing human CEA producing tumor were injected with rabbit anti-human CEA IgG labeled with glucose oxidase. The injection of antibody was following by an i.v. in jection of NaI. The rational for this approach was that the injected enzyme-labeled antibody will be deposited on the surface of CEA producing tumor cells and produces hydrogen peroxide, the hydrogen peroxide will oxidize the plasma membrane and become permeable to iodine ion and the iodine will kill the cells. It was found that the size of tumor was reduced significantly, but the mice underwent an insulin shock like hepoglycemia and CEA-enzyme labeled antibody immune complex were deposited on the glomerular basement membrance. To circumvent the problems, with this investigation, galactose oxidase was used in place of glucose oxidase and another cell surface antigen of which distribution will change as the CEA when the cell are transformed, but is insoluble in the plasma were sought. To obtain the antigen, a new isolation method for the brush border from colonic epithelial cells was developed, and from the isolated brush border, several brush border specific antigens with molecular weight of several thousand were identified. The utilization of cell surface antigens which are inaccessible to the circulation on normal epithelial cells, but become accessible upon transformation as the targets of immuno-targeted therpy does not require tumor specific antigens and the use of hydrogen peroxide labeled antibodies should avoid the systemic side effect of toxin labeled antibodies.
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