Data from Preclinical Evaluation of ON203, A Novel Bioengineered mAb Targeting Oxidized Macrophage Migration Inhibitory Factor as an Anticancer Therapeutic

• DOI: 10.1158/1535-7163.c.6603184
• Publication Date: 2023-04-17T18:46:02Z
• Authors: Gregor Rossmueller; Irina Mirkina; Barbara Maurer; Verena Hoeld; Julia Mayer; Michael Thiele; Randolf J. Kersch...; Alexander Schinagl

<div>Abstract<p>High levels of macrophage migration inhibitory factor (MIF) in patients with cancer are associated poor prognosis. Its redox-dependent conformational isoform, termed oxidized MIF (oxMIF), is a promising tumor target due to its selective occurrence lesions and at inflammatory sites. A first-generation anti-oxMIF mAb, imalumab, was investigated clinical trials advanced solid tumors, where it well tolerated showed signs efficacy. However, imalumab has short half-life humans, increased aggregation propensity, an unfavorable pharmacokinetic profile. Here, we aimed optimize by improving physicochemical characteristics boosting effector functions. Point mutations introduced into the variable regions reduced hydrophobicity antibodies’ potential, plasma accumulation <i>in vivo</i>, while retaining affinity specificity oxMIF. The introduction Fc region known increase antibody-dependent cellular cytotoxicity resulted enhanced functions novel antibodies vitro</i>, whereas cytokine release from human peripheral blood mononuclear cells absence antigen engineered mAb ON203 versus reveals favorable vitro</i> safety <i>In demonstrated superior efficacy over both prophylactic established prostate (PC3) mouse xenograft models. In summary, our data highlight potential second-generation as immunotherapy for warranting evaluation.</p></div>