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Gülçin Gezgin, Sietse J. Luk, Jinfeng Cao, Mehmet Dogrusoz, Danielle Krijgsman, Pieter A. van der Velden, Gregorius P. M. Luyten, J.William Harbour, Ekaterina S. Jordanova, Mirjam H. M. Heemskerk, Martine J Jager; PRAME: a potential target for immunotherapy in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) is the most common intraocular primary malignancy in adults. No effective therapies are yet available for metastatic disease. Preferentially-expressed antigen of melanoma (PRAME) is overexpressed in a variety of malignancies and could be a potential therapeutic target for TCR gene therapy when PRAME peptides are presented by HLA class I. The purpose of this study is to identify whether patients with UM metastases can be candidates for PRAME-specific TCR gene therapy.
Sixty-four enucleated eyes with primary UM were screened for PRAME gene expression with a RNA microarray. Tumors were dichotomized into low and high PRAME expressing tumors and clinical, histopathological and genetic parameters were compared between both groups. PRAME expression was determined by mRNA Fluorescent in situ hybridization (FISH) in 14 cases of primary UM and in 16 unrelated UM metastases. Additionally, HLA class I expression was determined in the metastases using triple immunofluorescence staining.
Twenty-nine primary UM had a high PRAME gene expression and 35 tumors had low PRAME gene expression. High PRAME expression in primary UM was associated with a larger basal diameter (p=0.005), more ciliary body involvement (p=0.008) and amplification of chromosome 8q (p=0.002). PRAME was present on the primary tumors in 7/14 cases and in 11/16 metastases. HLA class I was expressed in 10/16 metastases. In 8 of the 16 metastases cases concomitant HLA class I and PRAME were present.
PRAME is expressed on primary UM and UM metastases. In 50% of UM patients with metastases, PRAME and HLA class I expression occur together. Therefore, PRAME in UM metastases can be a target for PRAME-specific TCR gene therapy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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