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Development and characterization of antibodies to a nicked and hyperglycosylated form of hCG from a choriocarcinoma patient

Generation of antibodies that differentiate between pregnancy hCG and choriocarcinoma hCG

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Abstract

Human chorionic gonadotropin (hCG) exists in blood and urine as a variety of isoforms one of which contains peptide bond cleavages within its β-subunit loop 2 and is referred to as nicked hCG (hCGn). This hCG isoform appears to be more prevalent in the urine of patients with certain malignancies and possibly in some disorders of pregnancy. Until now, only indirect immunoassays could be used to quantify hCGn. We report the development of two monoclonal antibodies (MAbs) to a form of hCGn isolated from a choriocarcinoma patient. This hCG isoform was not only 100% nicked, but also contained 100% tetrasaccharide-core O-linked carbohydrate moieties in its β COOH-terminal region. Two-site immunometric assays have been developedusing these new antibodies, B151 and B152. The former exhibits good specificity for hCGn independent of the source of the hCGn, the form excreted by choriocarcinoma patients or the form of hCGn from normal pregnancies. The latter antibody, B152, is sensitive to the carbohydrate moieties and possibly other differences in hCG isoforms, but is not for nicking of the β-subunit. These two immunometric assays provide potential novel diagnostic tools for direct measurement of hCG isoforms which could not be accurately quantified earlier before development of the assays using these newly generated antibodies.

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Author notes

  1. Alexander Krichevsky

    Present address: KBL Technologies, Inc., 301 North Pasadana Dr., 15215, Pittsburgh, PA

Authors and Affiliations

  1. Department of Medicine, Columbia University College of Physicians and Surgeons, 10032, New York, NY

    Steven Birken, Alexander Krichevsky, John O’Connor, John Schlatterer & Robert Canfield

  2. Department of Pathology, Columbia University College of Physicians and Surgeons, 10032, New York, NY

    Steven Birken, Alexander Krichevsky, John O’Connor, John Schlatterer & Robert Canfield

  3. Department of Obstetrics and Gynecology, Yale University, New Haven, CT

    Laurence Cole & Andrew Kardana

Authors
  1. Steven Birken
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  2. Alexander Krichevsky
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  3. John O’Connor
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  4. John Schlatterer
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  5. Laurence Cole
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  6. Andrew Kardana
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  7. Robert Canfield
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Correspondence to Steven Birken.

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Birken, S., Krichevsky, A., O’Connor, J. et al. Development and characterization of antibodies to a nicked and hyperglycosylated form of hCG from a choriocarcinoma patient. Endocr 10, 137–144 (1999). https://doi.org/10.1385/ENDO:10:2:137

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  • DOI: https://doi.org/10.1385/ENDO:10:2:137

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