|Sidney Pestka, MD, professor and chair, Department of Molecular Genetics, Microbiology and Immunology, UMDNJ-Robert Wood Johnson Medical School|
In 1992, 63% of Americans diagnosed with cancer survived at least 5 years, according to the National Cancer Institute; that figure is estimated to be 67% for 2003. Considering that roughly 70 new cancer drugs were approved by the Food and Drug Administration (FDA) in the past two decades, and that the rate of approval has been increasing (27 drugs were approved from 1987 - 1996; and 43 drugs from 1997 - 2006), it is somewhat surprising that survival rates are not higher for the period from 1992 to 2003. If the many, new therapeutics are not sufficient to attack cancer effectively, we need to discern the reason. One possible explanation is that almost all cancer therapeutics are administered systemically. Because these drugs circulate throughout the body — and all produce a variety of side effects — the level of drugs administered must be limited to what the individual can tolerate, and the amount actually reaching the tumor may be insufficient to produce the desired results. There are only a few cancer therapies available that are able to be delivered directly to a tumor site. A wide variety of new methods are needed to deliver therapeutics directly to the tumor, thereby enabling higher doses of the drugs to be administered, and to reach and control or eliminate the cancer(s).
|Figure 1. Subcutaneous injection of interferon (or other drugs) into an individual distributes the therapeutics in the blood and other body fluids, with
relatively little of the
therapeutic agents residing on, in or near the tumors. The interferon is administered about three times per week, but some modified interferons are administered about once per week.
||Figure 2. Stem cells expressing interferons (or other therapeutics) could localize the interferons in the area of the tumor and the tumor environment. With little or no interferon in the general circulation, the side effects of the interferons will be minimized. Localization of the interferon in the vicinity of the cancer will enable high amounts of the interferons to destroy the tumors. The stem cells expressing the interferons are administered via intravenous injection once.|
Because bone marrow-derived mesenchymal stem cells (MSCs) have been shown to preferentially localize to the tumor stroma, stem cells expressing interferons might effectively deliver the interferons into the tumor tissues. Expressing highly potent interferons in tumors via stem cells would enhance the efficacy of the interferons to control and eliminate tumors by a wide variety of mechanisms such as direct antiproliferative activity, stimulation of the immune system, blocking angiogenesis, and converting tumor tissues into in situ vaccines. A major avenue for minimizing side effects is to localize the interferons in the tumors — a process that might be accomplished with stem cells. As cancers develop, they are filled with necrotic areas. Marrow-derived stem cells that are injected into animals or patients predominantly localize into the microenvironment of tumors. Thus, stem cells transfected with vectors expressing interferons could be used to deliver interferons directly into the tumors, and the side effects of interferon therapy would diminish. Minimization of these side effects could enable the interferons to be used to treat cancers effectively.
Sidney Pestka, MD, has been chair of the Department of Molecular Genetics, Microbiology and Immunology at UMDNJ-Robert Wood Johnson Medical School since 1986. He earned his MD from the University of Pennsylvania and his BA in chemistry from Princeton University summa cum laude. He was awarded the National Medal of Technology in 2002 by President George W. Bush for “pioneering achievements that led to the development of the biotechnology industry, to the first recombinant interferons for the therapy of cancers, leukemias, viral diseases such as hepatitis B and C, and multiple sclerosis, to fundamental technologies leading to other biotherapeutics; and for basic scientific discoveries in chemistry, biochemistry, genetic engineering and molecular biology from protein biosynthesis to receptors and cell signaling.”
He began his studies of interferon in 1969 at the Roche Institute of Molecular Biology. While there, he and his staff invented a method to isolate and purify interferon proteins — called reverse phase high-performance liquid chromatography — that is still used today; and his lab was the first to purify interferons alpha and beta, to clone them, and to identify their medical uses to fight viral diseases and cancer. In 1986, interferon alpha got the green light from the FDA to treat hairy cell leukemia; and later was approved to treat chronic hepatitis B and C, malignant melanoma, follicular lymphoma, some leukemias and AIDS-related Kaposi’s sarcoma. Since that time, interferon-based therapies have helped millions of people worldwide.
Dr. Pestka holds more than 100 U.S. and foreign patents, which are credited with laying the foundation for the multi-billion dollar biotherapeutics market, and he has written more than 400 published articles. He has also been recognized with the Warren Alpert Prize from Harvard University and the Lemelson-MIT Lifetime Achievement Award. He founded Pestka Biomedical Laboratories (PBL) in 1990, which provides high-quality, human interferons to researchers around the world and has patented “ultra interferons”—with 20 to 30 times more potency than those currently in use. With a longstanding conviction that the interferons are very powerful weapons against cancer, Dr. Pestka’s ultimate goal is to devise a method to deliver interferon therapy directly to the tumor site, thereby allowing much more potent forms to be used than can be tolerated systemically.