Research Papers:

Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer

Alexander Schinagl, Michael Thiele, Patrice Douillard, Dirk Völkel, Lukas Kenner, Zahra Kazemi, Michael Freissmuth, Friedrich Scheiflinger and Randolf J. Kerschbaumer _

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Oncotarget. 2016; 7:73486-73496. https://doi.org/10.18632/oncotarget.11970

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Alexander Schinagl1, Michael Thiele1, Patrice Douillard1, Dirk Völkel1, Lukas Kenner2,3,4, Zahra Kazemi5, Michael Freissmuth5, Friedrich Scheiflinger1, Randolf J. Kerschbaumer1

1Baxalta Innovations GmbH, Orth/Donau, Austria

2Department of Pathology, Medical University Vienna, Vienna, Austria

3Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria

4Institute of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria

5Institute of Pharmacology, Centre of Physiology and Pharmacology, Medical University, Vienna, Austria

Correspondence to:

Randolf J. Kerschbaumer, email: [email protected]

Keywords: MIF, cancer, inflammation, antibodies, drug target

Received: March 18, 2016     Accepted: September 02, 2016     Published: September 12, 2016


Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer.

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