A cell line designated RMG‐II was established from the ascites of a patient with ovarian clear cell carcinoma. The chromosomal analysis revealed aneuploidy with a hypertetraploid modal numher and 8 marker chromosomes. Radioimmunoassay and immunocytochemical staining showed that RMG‐II cells produced some tumor markers such as CA125 and TPA. Two monoclonal antibodies, designated MA602‐1 and MA602‐6, were generated by immunization of mice with an extract prepared from the culture supernatant of RMG‐II cells. The epitopes recognized by these two monoclonal antibodies were proved to differ from the CA125 epitope, but to exist on the molecule bearing CA125. We developed a double‐determinant sandwich enzyme imnnmoassay using these two monoclonal anti‐bodies, and the antigen defined by this assay was termed CA602. CA602 was frequently found in the sera of ovarian cancer patients; the positive rates were 92%, 38%, 60%, and 80% for serous, mucinous, clear cell, and endometrioid ovarian carcinomas, respectively, when the cut‐off value was set at 60 U/ml (=mean + 3SD of healthy females). CA602 levels in serum were also high in endometriosis patients and in early pregnancy, as is the case for CA125, and the correlation coefficient between CA602 and CA125 was high (r=0.88). Our preliminary evidence suggests that this CA602 assay system has higher sensitivity than the CA125 one.
The specificity of a tumor marker (CA54/61) and its individual epitopes (CA54 and CA61) recognized by monoclonal antibodies (MA54 and MA61) and expressed by the same tumor marker were studied. Serum levels of CA54 and CA61 were compared with that of CA54/61. In lung adenocarcinoma and ovarian carcinoma, the positive rates of CA61 (42% and 68%) were higher than those of CA54 (32% and 32%) and similar to those of CA54/61 (45% and 74%). The serum levels of CA54 and CA61 showed a significant correlation (r = 0.78), but 22% of tested sera were positive for CA54 and negative for CA61 or negative for CA54 and positive for CA61. It was demonstrated that the tumor specificity between CA54 and CA61 was not same and that the tumor specificity of CA54/61 was similar to that of CA61 rather than CA54. Moreover, the difference in the tumor specificity between CA54 and CA61 was considered to be reflected in the difference in their epitope structure.
An immunoenzymometric assay (IEMA) for a new CA125-like antigen, CA602, was developed. Five monoclonal antibodies raised against a human ovarian carcinoma cell line could detect their respective antigens in the sera of ovarian carcinoma patients. The antigen levels detected in serum by the various antibodies correlated significantly to each other, and to CA125 levels. The results of epitope analyses and combined IEMAs suggested that the epitopes recognized by these antibodies are not same, but exist on the same antigen which bears the CA125 epitope. A sensitive IEMA was developed with 602-1 and 602-6 antibodies which showed high reactivity to the CA125-like antigen. The antigen defined by these two antibodies was designated as CA602, and serum CA602 levels correlated well with CA125 levels. The CA602 antigen is a CA125-like antigen. Furthermore, the serum CA602 levels did not correlate to CA54/61 levels. The combined assays of CA602 and CA54/61 may increase the detection of ovarian carcinoma.
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