Immune Responses Induced by Anti-idiotypic Antibody against Anti-DU-PAN-2 Antibody and its application to Diagnosis and Therapy of Cancer
| Project/Area Number |
03454226
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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 |
Gastroenterology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SAWABU Norio Cancer Research Inst. Professor Department of Internal Medicine, がん研究所, 教授 (90019969)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Hideki Cancer Research Inst. Research Department of Internal Associate Medicine, がん研究所, 助手 (40203799)
SAKAI Shunnesuke Cancer Research Inst. Associate Department Immunobiology Professor, がん研究所, 助教授 (90092783)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | DU-PAN-2 Antigen / Anti-idiotypic Antibody / Serum Auto-antibody / Immune Response for Tumor / Monoclonal Antibody / Digestive Cancers / Tumor Marker / DUーPANー2抗原 / 単クロ-ン抗体 / 腫瘍マ-カ- |
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| Research Abstract |
Using monoclonal antibody (mAb) DU-PAN-2 as immunogen, we prepared polyclonal anti-idiotypic antibody (pId) in a rat and syngeneic monoclonal anti-idiotypic antibody (mId) by hybridoma technique. Since pId and mId reacted specifically with mAb DU-PAN-2 and inhibited the specific binding of DU-PAN-2 (D-2) antigen and mAb DU-PAN-2, mId and a certain portion of pId were considered to possess the mirror image of the determinant on the antigen defined by mAb DU-PAN-2. Immunization of syngeneic mice with mId induced anti-anti-Id antibodies (Ab3) which inhibited the binding of mAb DU-PAN-2 to the D-2 antigen. Moreover, Ab3 could not induced CDC activity and CTL, but ADCC activity.
An enzyme-linked immunosorbent assay (ELISA) utilizing these anti-idiotypic antibodies was developed and was used to examine the clinical significance of levels of circulating antibody against D-2 antigen in sera of cancers. With the mean + 2 SD of healthy controls regarded as the cutoff value, levels exceeded this value in 42% of cancer patients by pId assay, and in 33% by mId assay. The falsepositive rate of mId assay in benign diseases was 21% which was significantly lower than that of the pId assay (45%). No significant correlation between serum D-2 antigen and anti D-2 antibody was observed in the sera of cancer patients. 43% (pId assay), and 31% (mId assay) of the antigen negative cancer patients showed antibody levels exceeding the cutoff values. All of 12 patients with gastric or colonic cancer classified as histological stage I were negative for D-2 antigen, while 4 patients (33%) were antibody positive by pId assay. Anti-D-2 antibody fraction which was purified from the serum of a cancer patient by pId immunoaffinity chromatography, reacted with both D-2 antigen and mId as determined by various immunochemical techniques. Measurement of serum levels of anti-D-2 antibody may be useful in detecting malignancies including early of antigen-negative cancers.
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Report
(3 results)
Research Products
(25 results)
