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In vivo immuno-targ...
In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME)
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- Pankov, Dmitry (författare)
- Memorial Sloan-Kettering Cancer Center
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- Sjöström, Ludvig (författare)
- Memorial Sloan-Kettering Cancer Center,Lund University
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- Kalidindi, Teja (författare)
- Memorial Sloan-Kettering Cancer Center
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- Lee, Sang Gyu (författare)
- Memorial Sloan-Kettering Cancer Center
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- Sjöström, Kjell (författare)
- Innovagen AB
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- Gardner, Rui (författare)
- Memorial Sloan-Kettering Cancer Center
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- McDevitt, Michael R. (författare)
- Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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- O'Reilly, Richard (författare)
- Memorial Sloan-Kettering Cancer Center,Weill Cornell Medical College
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- Thorek, Daniel L J (författare)
- Johns Hopkins University School of Medicine
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- Larson, Steven M (författare)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Veach, Darren (författare)
- Weill Cornell Medical College,Memorial Sloan-Kettering Cancer Center
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- Ulmert, David (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Urologi, Malmö (Abrahamsson),Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Urological research, Malmö,Lund University Research Groups,Memorial Sloan-Kettering Cancer Center
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(creator_code:org_t)
- 2017-07-26
- 2017
- Engelska 15 s.
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:39, s. 65917-65931
- Relaterad länk:
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http://dx.doi.org/10...
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http://www.oncotarge...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Nyckelord
- Cancer
- Immuno-targeting
- Noninvasive imaging
- PRAME
- Targeted therapy
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Pankov, Dmitry
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Sjöström, Ludvig
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Kalidindi, Teja
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Lee, Sang Gyu
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Sjöström, Kjell
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Gardner, Rui
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visa fler...
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McDevitt, Michae ...
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O'Reilly, Richar ...
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Thorek, Daniel L ...
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Larson, Steven M
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Veach, Darren
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Ulmert, David
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Oncotarget
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Lunds universitet