In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME) Journal Article


Authors: Pankov, D.; Sjöström, L.; Kalidindi, T.; Lee, S. G.; Sjöström, K.; Gardner, R.; McDevitt, M. R.; O'Reilly, R.; Thorek, D. L. J.; Larson, S. M.; Veach, D.; Ulmert, D.
Article Title: In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME)
Abstract: Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is overexpressed in a broad range of malignancies, while absent in most healthy human tissues, making it an attractive diagnostic cancer biomarker and therapeutic target. Although commonly viewed as an intracellular protein, we have demonstrated that PRAME has a membrane bound form with an external epitope targetable with conventional antibodies. We generated a polyclonal antibody (Membrane associated PRAME Antibody 1, MPA1) against an extracellular peptide sequence of PRAME. Binding of MPA1 to recombinant PRAME was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). Flow cytometry and confocal immunofluorescence microscopy of MPA1 was performed on multiple tumor cell lines. Reverse Transcription Polymerase Chain Reaction (RTPCR) for PRAME was conducted to compare protein and transcriptional expression levels. We demonstrated a robust proof-of-concept for PRAME targeting in vivo by radiolabeling MPA1 with zirconium-89 (89Zr-DFO-MPA1) and demonstrating high specific uptake in PRAME expressing tumors. To our knowledge, this is the first time a cancer testis antigen has been targeted using conventional antibody technologies. Thus, PRAME can be exploited for multiple clinical applications, including targeted therapy, diagnostic imaging and treatment guidance in a widerange of malignancies, with minimal off-target toxicity. © Pankov et al.
Keywords: targeted therapy; cancer; noninvasive imaging; prame; immuno-targeting
Journal Title: Oncotarget
Volume: 8
Issue: 39
ISSN: 1949-2553
Publisher: Impact Journals  
Date Published: 2017-09-12
Start Page: 65917
End Page: 65931
Language: English
DOI: 10.18632/oncotarget.19579
PROVIDER: scopus
PMCID: PMC5630382
PUBMED: 29029482
DOI/URL:
Notes: Article -- Export Date: 2 November 2017 -- Source: Scopus
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