| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 1992: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1991: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Research Abstract |
In order to evaluate humoral immune response against cancer-associated carbohydrate antigens in patients with cancer, we tried to generate human monoclonal anti-carbohydrate antibodies and anti-idiotypic antibodies directed to them. Two human monoclonal antibodies, anti-S_<M4s> and anti-Lc_4 anti-bodies, were generated for this purpose. Since the Lc_4 antigen is widely expressed on human cancer cells, and there was less polymorphism in the immunoglobulin genes encoding human anti-Lc_4 antibodies, we established three murine monoclonal anti-idiotypic antibodies (G3, B3 and C5, all IgG) directed against the anti-Lc_4 antibody. When these anti-idiotypic antibodies were used for the detection of serum antibodies in patients with cancers, the C5 idiotype defined by the antibody C5 was found to be significantly in-creased in the sera of cancer patients than in the sera of control individuals. On the other hand, the G3 idiotype defined by the antibody G3 was found to be significantly decrease
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d in the sera of cancer patients than in the sera of control individuals, as ascertained by statistical analysis. Most of the V_H regions of human anti-Lc_4 antibodies were encoded by the germline gene V_H1.9III, while most of the V_<lambda> regions of human anti-Lc_4 antibodies were encoded by the germline gene V_<lambda>II.DS. The combination of V_H1.9III and V_<lambda>II.DS genes were widely used in encoding the antibodies directed to the antigens other than Lc_4. The C5 idiotope defined by the C5 antibody was specifically expressed by the anti-Lc_4 antibodies among these V_H1.9III-V_<lambda>II.DS encoded antibodies, while the G3 idiotope defined by the G3 antibody was widely expressed by these V_H1.9III-V_<lambda>II.DS encoded antibodies directed to the antigens other than Lc_4. These results suggest that the antibodies encoded by the combination of V_H1.9III and V_<lambda>II.DS genes are mostly used to encode antibodies directed to the Lc_4 antigen in patients with cancers which frequently express the antigen, while in patients without cancers, these genes are used freely to encode a wide variety of antibodies which are directed to various exogenous antigens other than the Lc_4 antigen. Less
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