Bench to Bedside: Target Cancer
How Bexxar became a guided missile against cancer cells
The Concept
The idea of attacking a cancerous cell with a man-made antibody wasn’t new in the late 1980s when Mark Kaminski, M.D., director, Leukemia/Lymphoma Program and Multidisciplinary Lymphoma Clinic, and Richard Wahl, M.D. (formerly at UMHS but now at Johns Hopkins), began applying this approach to non-Hodgkin’s lymphoma, a cancer of the immune system. The pair wondered if combining an antibody with a radioactive isotope would do a better job of killing these cancer cells, avoiding healthy cells and sparing patients the usual chemotherapy side effects of nausea and infection.
Non-Hodgkin’s lymphoma is the sixth leading cause of cancer death in the U.S. There are many different types of non-Hodgkin’s lymphoma and some are not considered curable by traditional methods.
Collaboration produces proof of concept
Kaminski and his team successfully created a radioactive antibody now named Bexxar® that seeks out cancerous lymphoma cells. It locks onto a specific protein on the cell surface and once attached to the cancer cells, the antibody packs a double punch. First, the immune system is signaled by the antibody to try to ‘gobble up’ the cancer.
Second, the iodine 131 in the antibody gives off radiation, one of the most effective treatments for this kind of cancer. Through this targeted approach, the cancer cells receive a greater concentration of therapeutic radiation while minimizing radiation exposure to normal tissues. In effect, the antibody is a guided missile.
Commercialization and FDA approval
The first steps to FDA approval and eventual commercialization began in April 1990, when Drs. Kaminski and Wahl began the first clinical trial with Bexxar at the University of Michigan. The trial was designed to show the safety and most effective dose. They eventually devised the treatment to include only two injections a week apart— far different from conventional treatments like chemotherapy that take months to complete.
The results were astonishing— four out of 10 patients had the tumor disappear completely!
Kaminski recalls being “absolutely delighted” by these results. “I remember standing next to Dr. Wahl looking at a CT scan of Patient #4. This gentleman had a two and a half pound mass in his abdomen before treatment and it disappeared. We knew we were seeing something very special.”
In 1993, Kaminski and Wahl, along with the U-M and Coulter Corporation—the manufacturer of the antibody at the time—were awarded patents on Bexxar. Eventually, a licensing agreement with GlaxoSmithKline was made. New studies were conducted around the country confirming the results and after more than a decade of testing, Kaminski saw Bexxar approved by the U.S. Food and Drug Administration on June 30, 2003, for the treatment of low-grade non-Hodgkin’s lymphoma—an incurable form of lymphoma—that no longer responds to conventional therapies.
In practice: from last-ditch effort to front-line choice
The Bexxar story continues to unfold. Not long after Bexxar’s proven success treating patients who no longer respond to conventional non-Hodgkin’s lymphoma therapies, Kaminski wondered if the regimen could be effective for patients as a first-line treatment, potentially offering a cure. It looks like he’s on the right track. Earlier this year, Kaminski and his team published a study showing dramatic results for patients using Bexxar as their
first line of treatment: 86 percent of patients treated with Bexxar survived after eight years of follownup, and half had not had a relapse of their disease.
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