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B. Esmaeli, M. D. Williams, A. Soheili, D. S. Gombos, R. Simantov; GPNMB Expression in Uveal Melanomas: A Potential for Targeted Therapy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3385.
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Uveal melanoma remains an aggressive disease without effective therapy for patients with metastatic or high risk disease. Despite clinical and genomic differences between cutaneous and uveal melanomas, shared biologic factors may lead to therapies which could benefit patients with melanoma regardless of origin. High expression of Glycoprotein NMB (GPNMB) in cutaneous melanomas led to CuraGen Corporation’s development of CR011-vcMMAE, a fully human monoclonal antibody (CR011) against the extracellular domain of GPNMB conjugated to a cytotoxic microtubule toxin monomethylauristatin E (MMAE). Ongoing Phase II trials suggest activity in advanced cutaneous melanomas with this novel targeted therapy. In an effort to determine the potential role of CR011 in uveal melanomas, we studied GPNMB expression in primary uveal tumors.
Paraffin tissue sections from 22 uveal melanomas treated by enucleation from 2004 to 2007 at M.D. Anderson Cancer Center formed were evaluated for immunohistochemical expression of GPNMB using biotinylated CR011 antibody and streptavidin-horseradish peroxidase detection. Melanoma cells were evaluated for staining intensity and percentage of cells with expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed.
22 patients (12 women, 10 men) with a median age of 58.7 years (range: 28 to 83yrs) were included. 18 of 21 tumors (85.7%) evaluable by immunohistochemical analysis (IHC) expressed GPNMB in 10-90% of tumor cells with variable intensity (6, 1+; 10, 2+; and 2, 3+; highest value in ≥5% of tumor cells). 11 of 18 tumors (61.1%) expressed GPNMB in ≥50% of the tumor cells. The specimen analyzed by spectral imaging showed CR011 reactivity in >50% of tumor cells.
Uveal melanoma commonly expresses GPNMB similar to cutaneous melanoma. CR011-vcMMAE is a novel targeted therapy to be further investigated for uveal melanomas in the metastatic and potentially also in the adjuvant setting.
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