SBIR-STTR Award

Mullerian Inhibiting Substance (MIS), a product of the fetal testis, is a high molecular weight glycoprotein that initiates regression of the Mullerian duct, the anlagen of the uterus, fallopian tube, and upper vagina. Biogen researchers have shown that this fetal regressor can also inhibit the growth of some tumors derived from the cell types which respond to the fetal regressor in embryonic life. Biologically active MIS has been purified 30,000-fold from bovine testis. However, the amount of bovine MIS that can be isolated by conventional means is too low to permit broad oncological studies, and the human protein is not available.Biogen proposes to use recombinant DNA technology to isolate the genes for bovine and human MIS and to express those genes in E. coli or animal cells. A process for purifying large amounts of human MIS in order to test the efficacy of MIS as an anticancer drug in a clinical setting will then be developed. Specifically in Phase I, peptides of bovine MIS and generate oligonucleotide probes will be sequenced. The probes will be used to isolate the bovine clone from a CDNA library, which will then be used to isolate the human gene.National Cancer Institute (NCI)

Mullerian Inhibiting Substance (MIS), a product of the fetal testis, is a 70 Kd glycoprotein that initiates regression of the Mullerian duct, the anlagen of the uterus, fallopian tube, and upper vagina. Biogen Research Corporation has shown that this fetal protein can also inhibit the growth of some tumors derived from cell types that 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, it is proposed to test the efficacy of MIS as an anticancer drug, scale up production of recombinant MIS, and conduct preclinical 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 preclinical testing.The results of this research will provide the basis for filing an Investigational New Drug (IND) application and permit the commencement of clinical trials in humans.National Cancer Institute (NCI)