With the help of the National Cancer Institute, we at Ibex Biosciences, propose the following Phase 1 SBIR project to evaluate novel camelid (VHH) antibodies that target macrophage migration inhibitory factor (MIF) for the treatment of solid tumors. MIF is known to play prominent roles in the development of cancer, and its expression in humans has shown to correlate with prostate cancer severity. Inhibition of MIF biologic activities using small molecule inhibitors or traditional antibodies may be found in the literature. However, there is only one anti-MIF candidate in the clinic. Additional approaches to anti-MIF treatments are therefore greatly needed. Use of a single chain antibody (VHH) for anti-MIF treatment offers many advantages over other therapeutic strategies, including increased stability and potential efficacy. We have therefore generated several anti-MIF VHH antibodies and produced preliminary data that warrant continued development efforts. The selected VHH have been demonstrated to bind MIF and preliminary cell-based assays show considerable anti-MIF. At Ibex Biosciences we wish to continue development of these anti-MIF VHH antibodies by establishing larger production levels of the VHH and test them in animal models. Our work will start with construction and expression of anti-MIF VHH and VHH-Fc antibodies. Succeeding feasibility work will focus on their characterization and demonstration of their functional antibody binding in cell line and animal models. While MIF has been demonstrated to play significant roles in many oncologic conditions, this evaluation will focus on prostate cancer for initial proof of concept. Subsequent development efforts will expand to other solid tumors such as pancreatic, lung, and others.
Public Health Relevance Statement: While progress in cancer treatment has been made, considerable unmet needs still exist. Macrophage migration inhibitory factor (MIF) is a key player in cancer pathophysiology, and its expression in humans has shown to correlate with prostate cancer severity. Anti-MIF antibodies may hold the key to treating prostate cancer. MIF represents a novel target for prostate cancer and VHH anti-MIF therapy offers new therapeutic possibilities.
Project Terms: Alpha Cell; Animal Model; Antibodies; Antibody Formation; Autoimmune Diseases; base; Binding; Biological Assay; Biological Factors; Biological Sciences; Biotechnology; Cancer Model; Cancer Patient; cancer therapy; Catalytic Antibodies; Cell Line; Cells; Characteristics; Chimeric Proteins; Clinic; Clinical; complementarity-determining region 3; Contract Services; Data; Delaware; Detection; Development; Diagnostic; Disease; DU145; Enzyme-Linked Immunosorbent Assay; Enzymes; Epitopes; Evaluation; experimental study; FLAG peptide; Functional disorder; gene therapy; Goals; Growth; Half-Life; Human; human migration; human monoclonal antibodies; improved; improved outcome; In Vitro; in vivo; Induction of Apoptosis; Inflammation; Light; Literature; Longevity; Lung; Malignant neoplasm of prostate; Malignant Neoplasms; Maryland; Medical; Migration Inhibitory Factor; Monoclonal Antibodies; mouse model; National Cancer Institute; novel; novel therapeutics; oncology; Pancreas; PC3 cell line; Phase; Phase I Clinical Trials; phenylpyruvate tautomerase; Play; polyhistidine; Preparation; Production; prostate cancer cell line; prostate cancer model; Prostate Cancer therapy; Proteins; Publications; Research; Role; Severities; Signal Transduction; Small Business Innovation Research Grant; small molecule inhibitor; Solid Neoplasm; Specificity; Stem cells; Technology; Testing; Therapeutic; Therapeutic antibodies; Treatment Factor; Western Blotting; Work; Xenograft procedure; Yeasts
