Monoclonal antibody-based biomarker targeting may be used for diagnosis, prognosis, and treatment of basal breast carcinoma.
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Overview Breast cancers are classified by their expression of estrogen receptors, progesterone receptors, and HER2. However basal breast carcinomas are clinically characterized as lacking these 3 main markers and are termed triple negative breast cancers (TNBCs). NBCs have a poor prognosis due to cancer recurrence caused by persistent cancer stem cells within the tumors. As a result, novel biomarkers are being sought for immune targeting and diagnosis of these high-risk cancers. The high molecular weight melanoma associated antigen (HMW-MAA) or chondroitin sulphate proteoglycan 4 (CSPG4), was recently found to be a highly specific marker for TNBCs and other cancers, including chordoma, melanoma and glioma. A team of University of Pittsburgh cancer immunologists have developed methods of using fully human monoclonal antibodies or antibody fragments specific for CSPG4 or HMW-MAA in therapeutic, prognostic and diagnostic applications. Antibody targeting of the CSPG4/HMWMAA biomarker may be used therapeutically in antibody-drug conjugates; to reduce metastasis in TNBCs; or to diagnose or provide prognoses on TNBCs and other CSPG4-expressing cancers. Applications • Reduce metastasis of triple negative breast cancers • Antibody-drug conjugates, targeted toxin therapy • Radio-immunoguided surgery • Imaging of primary tumors and metastases • Immunohistochemistry of formalin-fixed tissue • Western blot, flow cytometry Stage of Development • Pre-clinical animal studies Patents US 8, 486,393 US 9, 096,661 Effect of CSPG4–specific monoclonal antibody (mAb) on breast cancer cell growth, adhesion, and transmigration in vitro. J Natl Cancer Inst. 2010 Oct 6; 102(19): 1496–1512.