CIMIT-Russia Project:
A Russian-U.S. Collaboration for Production of Mullerian Inhibiting Substance (MIS)

Over 2.5 million people in the United States are diagnosed each year with ovarian, prostate, breast, endometrial or cervical cancer. Mullerian inhibiting substance (MIS), a protein involved with prenatal sexual differentiation, has been found to inhibit the growth of these types of cancers. MIS was first investigated more than 30 years ago by Dr. Patricia Donahoe of the Massachusetts General Hospital. In vitro and in vivo experiments performed by Donahue and her colleagues showed several years ago that MIS could be an effective treatment against ovarian cancer. More recently, they have demonstrated proof of principle for its efficacy in the treatment of other cancers of the sexual organs in animal models.

Because of its relatively large size and complexity, the production of significant quantities of recombinant MIS for clinical trials in humans is technically challenging and expensive. In the 1990s, a Massachusetts-based biotech company attempted to develop a commercial production process to make MIS, but found the technical and financial challenges too great. The CIMIT-Russia program has unique access to a number of former bioweapons institutions in Russia that possess sophistication in solving technical problems in recombinant protein production, and have significantly lower costs of operation. The CIMIT-Russia team has thus initiated a collaboration between scientists at one of these institutes—the State Research Institute of Highly Pure Biopreparations (SIRHPB) in St. Petersburg, Russia—and the Donahoe team at Massachusetts General Hospital (MGH) to address the technical problems of large scale production of MIS, which is a prerequisite for conducting therapeutic trials in humans.

At present, more than 40 Russian Ph.D.s at SRIHPB are working on this project. One team has already successfully replicated the methods used by the Donahoe lab to produce MIS in mammal cells, with an analogous yield. Other teams are initiating experiments with novel methods for producing MIS proteins in recombinant bacteria, yeast and fungi. Significant progress has already been made in a relatively short time. If any one of these new approaches is successful, it will reduce the costs of making this anti-cancer therapy. Recently, scientists from the Institute for the Chemistry of Plant Substances in Tashkent, Uzbekistan also joined the project to define transgenic methods of MIS production using silkworms.

If the MGH-SRIHPB team is successful in solving the technical problems of economical large-scale production of MIS, clinical investigators will soon be able to initiate phase I clinical trials of the protein in treating cancer. The intellectual property from this project will be shared by both institutions, resulting in new commercial opportunities for institutions in Massachusetts and Russia.