Stimulating the Immune System to Fight Cancer

Provenge and Yervoy for Prostate Cancer

PROVENGE. Dendreon Corporation

Over the last 30 years most attempts to harness the immune system to fight cancer have been disappointing.  We now know that these therapeutic attempts failed because they didn’t address the immune system’s innate ability to self-regulate; pushing the immune system to a higher level of activity instigates a natural push back from the immune system itself. This is a built-in safeguard against the immune system getting out of control.

Self-regulation quells the immune system from overactivity, preventing the development of serious immune diseases such as lupus, rheumatoid arthritis or multiple sclerosis. 

The latest research is now revealing that cancer exploits the regulatory component of the immune system to its advantage to fly under the radar and avoid being attacked by the killer T cells, the frontline soldier cells of the immune system. Thus cancer cells are essentially “cloaking” themselves from immune attack by “kidnapping” regulatory cells (Treg cells), using them as a shield to diminish the anticancer activity of the immune system, primarily the killer T cells.  Therefore, the latest research is showing that inability of the immune system to attack cancer does not come from any weakness of the immune system; rather, it is increased regulatory activity instigated by the cancer cells that is blocking killer T cell action against the cancer.


As it relates to fighting cancer, the immune system can be broken down into three major components: 1) the regulatory cells (Treg) that we have been discussing above; 2) killer T cells, the component of the immune system that directly attacks the cancer cells and kills them; and 3) the detector cells that ferret out the location of the cancer cells in the body and direct the immune system so it knows which cells to destroy.

These detector cells are called dendritic cells.  Dendritic cells, after they detect the location of the cancer, direct the killer cells to “home in” and attack the cancer. 

Combining two immune treatments that could work together simultaneously would seem to be a good way to further enhance the anticancer activity of the immune system. In fact, two immune-enhancing treatments are already FDA approved.

The first, Provenge, is FDA approved for the treatment of advanced prostate cancer. Two separate phase III trials have demonstrated that Provenge-treated men lived 20% longer compared to similar men treated with a placebo. Provenge works by stimulating the dendritic cells, i.e., providing a cancer “scent” that enables the killer T cells to better home in on the cancer. Provenge is the ultimate in personalized therapy because dendritic cells are filtered from the blood of each patient and then reinfused after they have been stimulated to a higher level of activity in the lab. 

The second immune medication is Yervoy.

  Yervoy is FDA approved for the treatment of melanoma, a cancer of the skin. Yervoy 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 Yervoy, the inhibitory action of the Treg cells is suppressed and the net effect is increased activity of the immune system.  Research with Yervoy in men with prostate cancer is ongoing and looks very promising. 

As exciting as both these intelligently designed therapies are as stand-alone treatments, the irresistible next step is to use them together to see if the anticancer benefit can be multiplied by using them in combination. Clinical trials are in progress. It seems very hopeful that the effectiveness of a well-tolerated immune treatment like Provenge will be much further enhanced when used in combination with a therapy like Yervoy that keeps the regulatory defenses of the Treg cells at bay.

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