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Conjugates of Elemental Selenium: A Novel Class of Cytotoxic Agents

MCW #1145


 Key Inventor

Fritz Sieber, PhD


This invention utilizes a carrier molecule such as recombinant human serum albumin (rHSA) and elemental selenium [Se(0)] particles for use as anti-cancer agents. Selenium is toxic if taken in large doses, but is an essential trace element in a healthy diet. Various selenium-based compounds have long been recognized for therapeutic applications in topical treatments and recently, research has focused on the use of selenium compounds as cytotoxic agents in the treatment of cancer. On the other hand, Selenium having an oxidation state zero [Se(0)] was thought to be biologically inert.

Research at The Medical College of Wisconsin demonstrates Se(0) has cytotoxic activity when introduced into cells. Furthermore, by introducing Se(0) into cells that are resistant to certain cytotoxic agents (e.g. ionizing radiation and alkylating agents) one can re-sensitize such cells to the cytotoxic agents. It is believed that the cytotoxic and cell-sensitizing activity of SE(0) relates to the intracellular depletion of reduced thiols and the accumulation of oxidized thiols.

The use of Se(0) as a therapeutic agent requires delivery with a carrier molecule such as Human serum albumin (HSA). HSA is the most well studied plasma protein and an attractive macromolecular carrier due to its availability in pure form (rHSA) and its biodegradability, non-toxicity and non-immunogenicity. For these reasons, it has been widely used as a stabilizing component in pharmaceutical and biologic products, such as vaccines, recombinant therapies and coatings for medical devices.

 Market Opportunity

Although HSA-SE0 addresses the multi-billion dollar anti-cancer market, it is believed that the drug will have the most benefit in treating multi-drug resistance and hematopoietic malignancies including lymphoma and leukemia. Multi-drug resistance is a significant problem in oncology as most patients become refractory to treatment after a few courses of treatment. Thus, almost all cancer patients can benefit by decreasing or eliminating multi-drug resistance. Currently, over 20 biotechnology and pharmaceutical companies are developing products for this indication. Similarly, in the US the annual incidence/mortality of Non-Hodgkin's Lymphoma and leukemia are approximately 56,000/23,500 and 37,000/23,000 respectively. As such, most companies with cancer products in development are looking at treatments for such hematopoietic malignancies.

 Stage of Development

This technology is at the feasibility stage of development. The cytotoxic activity of Se(0)-protein conjugates has been demonstrated through multiple in vitro studies. Animal studies are planned and will commence upon further funding.

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Summary Information

Patent Status:

Molecule Type:
Small Molecule

Patent Coverage Type:
Composition of Matter
Method of Use

Geographical Coverage:
US Patent

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