2000 Fiscal Year Final Research Report Summary
DEVELOPMENT OF A LUNG CANCER TREATMENT USING ANTI-KL-6/MUC1 MULTI-MONOCLONAL ANTIBODIES
| Project/Area Number |
10670548
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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 |
Respiratory organ internal medicine
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| Research Institution | HIROSHIMA UNIVERSITY (2000)
Ehime University (1998-1999) |
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Principal Investigator |
KOHNO Nobuoki HIROSHIMA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (80215194)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Akihito EHIME UNIVERSITY, MEDICAL HOSPITAL, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (30191513)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Lung Cancer / KL-6 / MUC1 / mouse monoclonal antibody / CAIMAN / human monoclonal antibody / chimera antibody / antibody supplement therapy |
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| Research Abstract |
MUC1 mucin, which is a membrane penetrating glycoprotein expressed on a variety of epithelial malignant cells, has a biological function to inhibit physically cell adhesion because of its length. We have clarified that a mouse monoclonal antibody, KL-6/MUC1 antibody, produced by us induces cell adhesion and suppress cancer cell proliferation. These results suppose that the supplementation of anti-KL-6/MUC1 antibodies might be effective as a new strategy against malignancies.
There are some problems in the application of mouse monoclonal antibodies to human being such as immunogenicity, deterioration of reactivity and metabolism. Humanization of mouse monoclonal antibodies, mouse-human chimera and CDR-grafted humanized antibody, have been attempted.
Cloning and the gene sequence analysis of cDNA, VH and Vκ genes, of the variable region of the KL-6/MUC1 mouse antibody was performed by the RT-PCR method using Mouse Ig-Primer set (Novagen, USA) after the extraction of RNA from KL-6/MUC1 mouse antibody producing hybridoma. Two different sequences were obtained both in VH and Vκ genes. Each one of the two was from P3/NS1/Ag-4-1 cell which is a parental murine myeloma cell of the hybridoma. The VH and Vκ genes were inserted into an expression vector which has the promotor and constant region arangements of human immunoglobulin. The reactivities of cloned humanized antibodies are examined.
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