BY MARK SCHOLZ
Using the immune system to fight cancer is a rapidly advancing area of research. The immune system (as it relates to fighting cancer) is made up of three components: 1) regulatory cells (TRegs), 2) killer cells, and 3) detector cells otherwise known as dendritic cells. Dendritic cells activate the killer cells and help them “home in” on the cancer.
Over the last 30 years, immune treatments have proven disappointing time after time due to a failure to address the immune system’s natural propensity of self-regulation. Self-regulation—inhibition of immune over-activity—is a normal aspect of immune function that prevents diseases such as lupus or multiple sclerosis.
However, recent research reveals that some cancers, prostate cancer being one of them, “cloak” themselves from immune attack by “kidnapping” TReg cells and using them as a shield to diminish or inhibit killer cell activity. This new understanding provides a good explanation of why the immune system fails to attack and eliminate cancer. Rather than being a type of weakness, immune inactivity is a type of blindness.
Two new treatments, one that is already FDA approved and another that is in Phase III trials, are designed to counteract this blindness; they are Ipilimumab and Provenge. Ipilimumab is a new drug from Bristol Myers that blocks an “on/off switch” on the surface of TReg cells. When the switch is in the on position TReg activity is up-regulated, suppressing the immune system. When the switch is locked in the off position by Ipilimumab, the inhibitory action of the TReg cells is taken off line. Ipilimumab was approved by the FDA in March 2011 to treat advanced melanoma. Preliminary studies of men with advanced prostate cancer have shown some dramatic results. In addition, Dr. Eugene Kwon from the Mayo Clinic has reported surprisingly good results against advanced prostate cancer using small doses of Ipilimumab in conjunction with hormone blockade. Presently two phase III trials of Ipilimumab in advanced prostate cancer are ongoing.*
Provenge was FDA approved to treat advanced prostate cancer in 2010 after two separate phase III trials showed that Provenge-treated men lived 20% longer than men treated with a sham infusion. Provenge works by providing a cancer “scent” (via a common cancer protein called PAP) to activate the dendritic cells and enable them to better home in on the cancer. Provenge is the ultimate individualized therapy because dendritic cells are filtered from the blood of each patient and exposed to PAP in the laboratory. Each patient’s own activated dendritic cells are then reinfused back into the blood stream.
As exciting as both these intelligently designed therapies are as stand-alone treatments, the irresistible next step is to use them together. It is natural to assume that the effectiveness of a well-tolerated treatment like Provenge will be further enhanced when used in combination with a therapy like Ipilimumab that will keep the regulatory defenses of the TReg cells in check. I contacted Bristol Myers this week to inquire about the status of research into the effectiveness of a Provenge/Ipilimumab combination. I was assured that such a study is in the works and anticipated to become a reality in the near future.
*Prostate Oncology Specialists is conducting two Ipilimumab trials in advanced prostate cancer. Parties interested in participating in one of these trials in Marina del Rey, may contact Jennifer at (310)827-7707 or jennifer@prostateoncology.com. Additionally, you may visit http://ResearchForProstateCancer.com
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