Mullerian Inhibiting Substance (MIS), a product of the fetal testis, is a 70 Kd glycoprotein which initiates regression of the Mullerian duct, the anlagen of the uterus, fallopian tube, and upper vagina. Donahoe and co-workers have shown that this fetal protein also can inhibit the growth of some tumors derived from cell types which respond to the fetal regressor in embryonic life. Thus, MIS may prove to be an effective treatment for gynecologic tumors. However, the human protein is very rare. During Phase I, the human MIS gene was isolated and expressed in animal cells, providing the technology for producing large amounts of human MIS. In Phase II, we propose to test the efficacy of MIS as an anti-cancer drug, scale up production of recombinant MIS, and conduct pre-clinical tests. Specifically, studies during the first year will focus on purifying small amounts of MIS (10 mg) and demonstrating antiproliferative effects against tumors in vitro in tissue culture and in vivo in animals. During the second year, large amounts of MIS will be produced and purified (10 g) for pre- clinical testing. The results of this research will provide the basis for filing an IND and permit the commencement of clinical trials in humans.
