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Immune Responses Induced by Anti-idiotypic Antibody against Anti-DU-PAN-2 Antibody and its application to Diagnosis and Therapy of Cancer

抗独特型抗体抗DU-PAN-2抗体诱导的免疫反应及其在癌症诊断和治疗中的应用

基本信息

批准号：
03454226
负责人：
SAWABU Norio
金额：
$ 3.01万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

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.

以单克隆抗体DU-PAN-2为免疫原，用杂交瘤技术制备了大鼠抗独特型多克隆抗体（pId）和同系单克隆抗独特型抗体（mId）。由于pId和mId与mAb DU-PAN-2特异性反应并抑制DU-PAN-2（D-2）抗原与mAb DU-PAN-2的特异性结合，因此认为mId和pId的某一部分具有mAb DU-PAN-2所定义的抗原上决定簇的镜像。用mId免疫同系小鼠诱导抗-抗-Id抗体（Ab 3），其抑制mAb DU-PAN-2与D-2抗原的结合。利用这些抗独特型抗体建立了酶联免疫吸附试验（ELISA），并用于检测恶性肿瘤患者血清中抗D-2抗原循环抗体水平的临床意义。以健康对照的平均值± 2 SD作为截止值，通过pId测定，42%的癌症患者的水平超过该值，通过mId测定，33%的癌症患者的水平超过该值。良性疾病中mId的假阳性率为21%，明显低于pId的假阳性率（45%）。肿瘤患者血清中D-2抗原与抗D-2抗体之间无明显相关性。43%（pId测定）和31%（mId测定）的抗原阴性癌症患者显示抗体水平超过临界值。12例组织学I期胃癌或结肠癌患者D-2抗原均为阴性，4例（33%）pId抗体阳性。用pId免疫亲和层析法从癌症患者血清中纯化的抗D-2抗体组分，经各种免疫化学技术测定，与D-2抗原和mId均反应。血清抗D-2抗体水平的测量可能有助于检测恶性肿瘤，包括抗原阴性的早期癌症。