A Research Tool for Elucidating the Interaction Between Human Mucin 16 (Ca-125) and Immune Cells in Ovarian Cancer

Kornel Lakatos, MD
Department of Obstetrics and Gynecology
Division of Medical Oncology
Poster Overview

Ca-125 is a protein component of MUC 16 and measured by an assay developed in 1982. High levels of CA-125 predict adnexal masses more likely to be malignant and correlates with poorer prognosis for ovarian cancer. Rising level after treatment suggests recurrence. Ovarian tumor cells produce and shed MUC 16 which can bind to certain peripheral immune cells. To study this, current techniques use labelled-fluorecent markers that bind to CA-125 on cells and flow cytometry to detect it. A limitation is that this technique may not be able to distinguish low-binding events from autofluorescence. Our new technology uses: darkfied microscopy rather than flow, antibody-labelled gold nanoparticles with far-greater sensitivity than fluorecent markers, automated slide scanning and focusing for 3 dimensional counting, ability to simultaneoulsy detect fluorescent markers to identify cells with Ca-125-binding, and automated image analysis. This new imaging system was developed in collaboration with PNPResearch Corporation, Brigham and Women’s Hospital, Kevin Elias Laboratory, Massachusetts General Hospital, University of Wisconsin Medical School and Thorlabs Inc. Preliminary data show that MUC 16 is preferentially bound to NK and T cells in women with ovarian cancer compared to binding in healthy controls.

Scientific Abstract

Ca-125 is a protein component of MUC 16 and measured by an assay developed in 1982. High levels of CA-125 predict adnexal masses more likely to be malignant and correlates with poorer prognosis for ovarian cancer. Rising level after treatment suggests recurrence. Ovarian tumor cells produce and shed MUC 16 which can bind to certain peripheral immune cells. To study this, current techniques use labelled-fluorecent markers that bind to CA-125 on cells and flow cytometry to detect it. A limitation is that this technique may not be able to distinguish low-binding events from autofluorescence. Our new technology uses: darkfied microscopy rather than flow, antibody-labelled gold nanoparticles with far-greater sensitivity than fluorecent markers, automated slide scanning and focusing for 3 dimensional counting, ability to simultaneoulsy detect fluorescent markers to identify cells with Ca-125-binding, and automated image analysis. This new imaging system was developed in collaboration with PNPResearch Corporation, Brigham and Women’s Hospital, Kevin Elias Laboratory, Massachusetts General Hospital, University of Wisconsin Medical School and Thorlabs Inc. Preliminary data show that MUC 16 is preferentially bound to NK and T cells in women with ovarian cancer compared to binding in healthy controls.

Clinical Implications
Earlier detection of ovarian cancer. More accurate and sensible monitoring of the success of ovarian cancer treatment.
Research Areas
Authors
Kornel Lakatos, German Gonzalez, Petra Krauledat, Daniel W Cramer, Kevin Elias, Manish S Patankar, Peter Hansen
Principal Investigator
Kevin Elias

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