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

Pankov, Dmitry; Sjöström, Ludvig; Kalidindi, Teja; Lee, Sang Gyu; Sjöström, Kjell; Gardner, Rui; McDevitt, Michael R.; O'Reilly, Richard; Thorek, Daniel L J and Larson, Steven M, et al. (2017) In Oncotarget 8(39). p.65917-65931
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... (More)

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.

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published
subject
keywords
Cancer, Immuno-targeting, Noninvasive imaging, PRAME, Targeted therapy
in
Oncotarget
volume
8
issue
39
pages
15 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85030093422
ISSN
1949-2553
DOI
10.18632/oncotarget.19579
language
English
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yes
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a515188c-37b9-4c1c-811e-430dd725d012
date added to LUP
2017-11-07 15:06:36
date last changed
2018-01-16 15:27:19
@article{a515188c-37b9-4c1c-811e-430dd725d012,
  abstract     = {<p>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 (<sup>89</sup>Zr-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.</p>},
  author       = {Pankov, Dmitry and Sjöström, Ludvig and Kalidindi, Teja and Lee, Sang Gyu and Sjöström, Kjell and Gardner, Rui and McDevitt, Michael R. and O'Reilly, Richard and Thorek, Daniel L J and Larson, Steven M and Veach, Darren and Ulmert, David},
  issn         = {1949-2553},
  keyword      = {Cancer,Immuno-targeting,Noninvasive imaging,PRAME,Targeted therapy},
  language     = {eng},
  number       = {39},
  pages        = {65917--65931},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME)},
  url          = {http://dx.doi.org/10.18632/oncotarget.19579},
  volume       = {8},
  year         = {2017},
}