In one of the most encouraging cancer vaccine therapy trials to date, researchers from the University of Chicago and Genetics Institute (Cambridge, MA) have demonstrated that their faster, simpler and safer approach to treatment may also be more effective than previous cancer vaccines. By giving melanoma patients the immune stimulant interleukin-12, the researchers were able to bypass the costly and difficult process of growing large populations of dendritic cells in culture and returning them to the patient, a process that takes weeks.
Instead, they extracted circulating white blood cells, exposed them to either of two markers commonly seen on melanoma cells, and returned them to the patient -- a process that takes only a few hours. Then they gave the patients different doses of IL-12 over the next five days to boost the immune response. The treatment cycle was repeated three times.
"Using total white blood cells instead of cultured dendritic cells was somewhat heretical," explains Thomas Gajewski, M.D., Ph.D., assistant professor of pathology and medicine at the University of Chicago and director of the study, "but our results indicate that it can be just as effective yet avoids the risks, delays and complexity associated with growing dendritic cells in culture."
The key finding, presented May 17th at the annual meeting of the American Society of Clinical Oncology in Atlanta, was the surprise discovery that moderate doses of IL-12 were far more effective at stimulating an anti-cancer response than higher, more-toxic doses.
Phase-1 clinical trials are usually designed to determine the maximum tolerated
dose of a new drug, but this trial indicated that the best dose was about one
tenth of the maximum dose -- suggesting that dosing trials of biologic therapies
require a radically different design. At moderate doses, IL-12's most serious
side effects were tenderness at the injection site, tiredness and mild fever.
Higher doses were more toxic and m
Contact: John Easton
University of Chicago Medical Center