Drake: "Significant anti-tumor effects."
Scientists studying many forms of cancer believe that cancer vaccines – which boost the body's immune system so that it can lead a "home front" strike against cancer cells – hold great promise. GVAX Prostate is a cell-based vaccine, originally developed at Johns Hopkins, that may help the body target and kill prostate cancer cells. By itself, it is not enough to vanquish metastatic prostate cancer; thus, scientists have been studying ways to combine it with other forms of immune-based therapy to create a multi-pronged attack. Recently, Ipilimumab, a drug that blocks a particular checkpoint in the immune system, called CTLA-4, was approved by the FDA for the treatment of metastatic melanoma. This CTLA-4 blocker (anti-CTLA-4) "has been shown to have powerful anti-cancer effects in some patients with melanoma, and to decrease PSA in some late-stage prostate cancer patients," says Charles Drake, M.D., Ph.D., associate professor of oncology, immunology and urology.
"However, it has also been associated with a significant risk of autoimmune toxicity." In addition, the response rate, or how often actual tumor shrinkage occurs, is less than 20 percent even in melanoma. Based on these findings, one way to optimize immune treatment for prostate cancer might be to combine a cancer vaccine like GVAX with a second immune-activating agent like Ipilimumab.
In recent preclinical studies, Drake and colleagues combined CTLA-4 blockade with GVAX and discovered that it’s important to follow the recipe: "We found that the order in which the agents are administered is critical, in that anti-CTLA-4 increases vaccine activity only when it’s given soon after the GVAX vaccine," Drake says. "When the proper sequence is followed, one can see significant anti-tumor effects, even at low doses of anti-CTLA4. This could potentially lead to greater efficacy with fewer side effects." This research, supported by the Patrick C. Walsh Prostate Cancer Research Fund, was published in the Journal of Translational Medicine. "To our knowledge, this is the first study to report extensively on the importance of timing and dosage in this kind of a treatment regimen."
"The combined approach boosts
the immune system in two ways."
In other news, Drake and colleagues have developed a mouse model of prostate inflammation that promises to be of great help to scientists studying benign enlargement of the prostate (BPH) and prostatitis. "This could turn out to be a really nice model of chronic inflammatory prostatitis," says Drake. "Some men with inflammatory prostatitis have active inflammation in the absence of infection, which makes us think that it’s caused by an autoimmune response. Unfortunately, this group of patients is the most difficult to treat. New insights into this disease process could lead to new ways to treat it, which are desperately needed." This work, by Drake and scientists currently at Yale University, Vanderbilt University Medical Center, University of Pittsburgh Medical Center, and Penn State Mont Alto, was published in The Prostate.