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bioRxiv · 10.1101/2023.02.08.527749

Individual recombinant repeats of MUC16 display variable binding to CA125 antibodies

Wang, C.-W.·Hanson, E. K.·Minkoff, L.·Whelan, R. J.
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Abstract

BACKGROUNDDespite its importance in the clinical management of ovarian cancer, the CA125 biomarker--located on the mucin protein MUC16--is still not completely understood. Questions remain about MUC16s function and structure, specifically the identity and location of the CA125 epitopes. OBJECTIVEThe goal of this study was to characterize the interaction of individual recombinant repeats from the tandem repeat domain of MUC16 with antibodies used in the clinical CA125 II test. METHODSUsing E. coli expression, we isolated nine repeats from the putative antigenic domain of CA125. Amino acid composition of recombinant repeats was confirmed by high-resolution mass spectrometry. We characterized the binding of four antibodies--OC125, M11, "OC125-like," and "M11-like"--to nine recombinant repeats using Western blotting, indirect enzyme-linked immunosorbent assay (ELISA), and localized surface plasmon resonance (SPR) spectroscopy. RESULTSEach recombinant repeat was recognized by a different combination of CA125 antibodies. OC125 and "OC125-like" antibodies did not bind the same set of recombinant repeats, nor did M11 and "M11-like" antibodies. CONCLUSIONSCharacterization of the interactions between MUC16 recombinant repeats and CA125 antibodies will contribute to ongoing efforts to identify the CA125 epitopes and improve our understanding of this important biomarker.

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Wang, C.-W., Hanson, E. K., Minkoff, L., Whelan, R. J.. 2023-02-09. Individual recombinant repeats of MUC16 display variable binding to CA125 antibodies. https://doi.org/10.1101/2023.02.08.527749

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