March 23, 2009 - By Janelle Weaver
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STANFORD, Calif. - The development of a drug that has revolutionized the treatment of many types of cancer has earned its inventor, Ronald Levy, MD, the 2009 King Faisal International Prize in Medicine.
More than 30 years ago, Levy, now chief of the oncology division at the Stanford University School of Medicine, embarked on a research agenda that harnessed the power of the body's own immune system to fight cancer. Levy developed the concept that a drug made from a naturally produced blood protein called an antibody could be a cancer-fighting machine.
On March 29, Levy, who holds the Robert K. and Helen K. Summy Professorship at Stanford, will be honored for this seminal discovery by Saudi Arabian royalty, who will present Levy with his most prestigious international award to date.
Rituxan, the drug that resulted from Levy's work, was approved by the Food and Drug Administration in 1997, making it the first commercial antibody to treat cancer. "Now it's recommended for treating almost every lymphoma patient, and over 1 million people have been treated with it so far," he said.
According to Levy, when combined with other drugs and radiotherapy, Rituxan is successful at reducing tumor size in most patients who are treated. Originally developed for the treatment of lymphoma, a cancer of the immune system, this class of drug is now part of the standard treatment for a wide range of cancers, including cancer of the breast, colon and lungs. "Monoclonal antibodies have transformed the way cancer is treated," said Levy, who is a member of the Stanford Cancer Center.
Levy joins the elite rank of 19 Americans who have received King Faisal International Prizes in Medicine since they were first awarded in 1982. The King Faisal Foundation, a philanthropic organization founded in 1976 by the eight sons of the late King Faisal bin Abdulaziz Al Saud, awards approximately five prizes each year to those who make notable contributions in the fields of Islamic studies and service, Arabic language and literature, science and medicine.
"I was nominated by Dean Pizzo for the Faisal award at least eight or nine months ago. He asked for my permission, and I said ‘OK,'" said Levy, recounting the conversation with Philip Pizzo, MD, the medical school's dean. "I didn't think it was very likely that I would be chosen. By the time I found out, my picture was already on the foundation's Web site."
Levy's efforts have focused on treating lymphoma. Forming the backbone of the immune system are B-lymphocytes - white blood cells that sound the alarm in response to foreign invaders. When a pathogen enters the body, B cells produce antibodies, proteins that circulate throughout the bloodstream and mark pathogens for destruction. In lymphoma, these B cells multiply uncontrollably, eventually crowding out healthy cells.
"Dr. Ron Levy is one of the most remarkable and accomplished physician-scientists in the world," said Pizzo. "With nearly laser-like focus he has dedicated his illustrious career to unraveling innovative ways of treating malignant lymphomas. He and his colleagues have virtually transformed our knowledge about tumor immunology and cancer biology, and his research has resulted in dramatic improvements in the treatment and survival of patients with lymphoma."
Rituxan targets a protein, called CD20, found on the surface of normal B cells and present in many lymphoma tumors. The prevalence of CD20 makes the drug relatively economical: it is not necessary to concoct a custom-made antibody for each patient. Although Rituxan targets normal B lymphocytes in addition to the tumor cells, it causes fewer side effects than conventional cancer treatments. Surprisingly, the drug results in no permanent damage to the immune system.
Two scientists working in England paved the way for Levy's cancer treatment successes. In 1975, Georges Koehler, PhD, and Cesar Milstein, PhD, created what they called hybridomas. "They glued antibody-making cells together with cancer cells to produce hybridomas, which lived forever and provided a permanent supply of monoclonal antibody," said Levy.
Hybridomas could be used to continually mass produce very specific antibodies that could target a particular marker, such as a protein that is present only on cancer cells. "With this discovery, I realized there was a potential for therapeutic uses. I decided to use this approach against cancer cells, and it actually worked," Levy said. Together with Richard Miller, MD, then a fellow in oncology and now an adjunct clinical professor of oncology at Stanford, and David Maloney, MD, PhD, then a Stanford medical student and now a professor of oncology at the University of Washington, Levy injected monoclonal antibodies made from mouse hybridoma cells into humans, and those monoclonal antibodies eliminated the cancer cells but not normal cells.
In 1981, Levy and his team cured their first patient, and four years later they started a company, called IDEC Pharmaceuticals, initially to make custom antibodies for each patient. The team soon realized that customizing monoclonal antibodies for each patient was too technically challenging, slow and expensive. That's when they started to work on what eventually became Rituxan.
To celebrate his research achievement, Levy will travel to Riyadh to receive a certificate written in Arabic calligraphy describing his work, a commemorative 24-carat, 200-gram gold medallion and $200,000. In his speech, he will recount the nature of his work and its impact. He will also emphasize that cancer is a universal problem and the solution crosses boundaries of cultural, national, ethnic and religious identity. "The problem of cancer has not been solved. That will require a lot more hard work involving international collaborations," said Levy.
Although Levy has received numerous honors and awards, from being a member of the National Academy of Sciences to receiving the Medal of Honor from the American Cancer Society, he recognized the uniqueness of the Faisal Prize. "It transcends beyond science and medicine alone. It has a cross-cultural aspect, and it offers a special opportunity to make an impact beyond science."
Levy's current research focuses on developing vaccines to treat cancer. "A vaccine would teach the immune system to launch its own battle on cancer. The advantage of the vaccine is that you'd only have to administer it once, and it includes a complex mixture that will trigger a multifaceted response all at once," he said.
"We have not come as far as we would like; we have a lot further to go," he said. "The immune system is very powerful, and I would like to harness even more power from it. But that's only one approach. I would like to combine it with other approaches, some yet to be discovered - that's the exciting part."
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