By tripping two parallel "on switches" at once, instead of the customary single switch, physicians at the University of Chicago Medical Center may at last have found a way to bring the full power of the immune system into play against cancer. Early results from the first clinical trial of this approach will be presented December 5th at the American Society of Hematologists meeting in Miami Beach, Florida.
This phase-1 clinical trial -- designed not to assess effectiveness but to determine the optimal dose and measure toxicity -- involved patients with advanced or recurrent lymphoma who had not responded to prior chemotherapy. Although patients in phase-1 studies like this rarely have a lasting recovery, several of those enrolled in this trial have experienced noteworthy anti-tumor effects.
"When you consider that none of these patients had responded to any other therapy, you can begin to understand our enthusiasm," said David Liebowitz, M.D., Ph.D., director of stem-cell transplantation at the University of Chicago and principal investigator of the study. "Although this is a complex and difficult treatment regimen, all the early signs suggest that it can be a uniquely effective one."
The treatment is based on recent recognition of the importance of "co-stimulation" in triggering an immune response. Previous efforts to activate the immune system have relied on stimulation of a single signaling system, the T-cell receptor for antigen, known as CD3, a cell-surface molecule that recognizes foreign tissue.
Nearly ten years ago, however, Chicago researchers Craig Thompson and Jeffrey
Bluestone and others discovered that the immune system often requires two
parallel lines of communication -- through both CD3 and a second receptor, known
as CD28 -- before girding for battle. Stimulation of both CD3 and CD28 triggers
an aggressive immune response; tweaking only CD3 produces little or no respo
Contact: John Easton
University of Chicago Medical Center