Target Therapy for Ovarian Cancer
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Ovarian cancer is frequently diagnosed in advanced stages of the disease, resulting in a high incidence of poor prognosis for the patient. Current therapies including surgery, chemotherapy, radiotherapy, and immunotherapy are often inadequate to overcome the disease. New therapeutic strategies are needed to treat ovarian cancer. A potential target for ovarian cancer therapeutics is Mullerian inhibiting substance (MIS) and its receptor, Mullerian inhibiting substance type II receptor (MISIIR). MIS and MISIIR are involved in Mullerian duct regression during the development of male reproductive organs. It has been shown that human MISIIR is expressed in a large percentage of ovarian surface epithelium and ovarian cancer cells and that exposure of ovarian cancer cells to MIS can inhibit their growth.
The goal of this research was to generate antibodies that bind specifically to MISIIR and trigger the regression of ovarian tumors. Recombinant human MISIIR extracellular domain-human Fc domain fusion proteins were used to select for MISIIR specific human single-chain variable fragments (scFv) in a human nonimmune scFv phage display library. The identified clones were then utilized to design bivalent scFv:Fc antibody-based molecules that bound specifically to human ovarian cancer cells.
MISIIR antibody constructs will provide a highly specific means of targeting MISIIR on human ovarian carcinoma cells for the purpose of diagnosing and treating ovarian cancer. The antibody could function as an MIS ligand, inducing downstream signaling pathways. This is beneficial, as MIS itself has proven to be difficult to produce in large quantities. The design of the antibody containing an IgG Fc domain will prolong its time in circulation and can induce tumor cell killing via antibody dependent cell cytotoxicity or complement dependent cytotoxicity.
U.S. and foreign patent applications pending.
Animal Model: MISIIR-TAg Mouse - A New Model of Epithelial Ovarian Cancer
For licensing information, contactInna Khartchenko
Associate Director, Office of Corporate Alliances Fox Chase Cancer Center
610 Old York Road, Suite 400
Jenkintown, PA 19046