title: Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer.
abstract: 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.
authors.affiliation: Baxalta Innovations GmbH, Orth/Donau, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schinagl
authors.affiliation: Baxalta Innovations GmbH, Orth/Donau, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Thiele
authors.affiliation: Baxalta Innovations GmbH, Orth/Donau, Austria.
authors.forename: Patrice
authors.initials: P
authors.lastname: Douillard
authors.affiliation: Baxalta Innovations GmbH, Orth/Donau, Austria.
authors.forename: Dirk
authors.initials: D
authors.lastname: Völkel
authors.affiliation: Department of Pathology, Medical University Vienna, Vienna, Austria.|Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.|Institute of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.affiliation: Institute of Pharmacology, Centre of Physiology and Pharmacology, Medical University, Vienna, Austria.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kazemi
authors.affiliation: Institute of Pharmacology, Centre of Physiology and Pharmacology, Medical University, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Freissmuth
authors.affiliation: Baxalta Innovations GmbH, Orth/Donau, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Scheiflinger
authors.affiliation: Baxalta Innovations GmbH, Orth/Donau, Austria.
authors.forename: Randolf J
authors.initials: RJ
authors.lastname: Kerschbaumer
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008263:Macrophage Migration-Inhibitory Factors
keywords: MIF; antibodies; cancer; drug target; inflammation