PITTSBURGH, May 17 -- For the first time, investigators have correlated the use of interferon alfa 2b (IFNa2b) with specific immune responses in patients treated with high doses of this agent to prevent the recurrence of melanoma. These findings, part of a landmark multi-center study based at the University of Pittsburgh Cancer Institute (UPCI), begin to account for the impact of IFNa2b on relapse-free survival among study patients. The results shed light on how this biological therapy works and provide signposts that could one day help clinicians pinpoint which patients will benefit from therapy, according to the investigators, who are presenting their preliminary findings Monday, May 17, at the annual meeting of the American Society of Clinical Oncology in Atlanta.
"This is the first attempt to make immunologic sense of the effects of IFNa2b on patients receiving this drug to prevent the recurrence of melanoma," said John Kirkwood, M.D., professor of medicine at the University of Pittsburgh and director of UPCI's Melanoma Center. "We found evidence that high-dose IFNa2b modulated the body's expression of cell markers called MHC Class II antigens on tumor tissues. These markers are necessary for the anti-tumor activity of one group of immune cells, or helper T cells. High-dose interferon also increased the response of a special set of immune cells, called natural killer cells, which may be more broadly active against melanoma cells."
Interferons are biological response modifiers produced naturally by the body to fight infections and tumors. IFNa2b is manufactured for use in cancer treatment studies, and can cause flu-like symptoms and depression in people receiving it.
The immunologic findings were made during a large study of high-dose IFNa2b, low-dose IFNa2b or observation for patients with surgically removed melanoma considered at high risk of recurrence. Results of this study have shown that recipients of a yearlong course of high-dose IFNa2b are more likely to remain free of disease than counterparts who receive low-dose IFNa2b or no therapy at all after initial surgery.
"By knowing how the immune system of a melanoma patient typically responds to high-dose IFNa2b within a few months of administration, we may better select patients who are likely to benefit from this therapy and steer those patients who are not responding using these parameters to other therapies that may provide them a greater benefit," added Dr. Kirkwood.
Dr. Kirkwood and Hassane Zarour, M.D., a UPCI research associate who is presenting this study at the ASCO meeting, are extending their research in recipients of high-dose IFNa2b to look for tumor antigens that may play a role in up-regulating the expression of class II MHC to better stimulate the anti-cancer activity of helper T cells.
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