In my last blog I contended that of all the different ways to treat cancer—hormone therapy, chemotherapy, radiation or surgery for example—immune therapy has the greatest potential to save lives: Only the immune system, by its very nature, has the ability to adapt to the many thousands of varieties of cancer. Also, new breakthroughs in understanding how it works have led to real progress inharnessing the immune system to fight cancer.
One discovery—that the immune system uses a specific type of immune cell called the “dendritic cell” to detect cancercells—led researchers at a company called Dendreon to develop a five-step process for enhancing dendritic cell function.
First the dendritic cells are filtered out of the blood for processing in the lab. Second, the dendritic cells are exposed to prostatic acid phosphatase (PAP), a protein that can be identified on the surface of almost all prostate cancer cells. Third, the dendritic cells are incubated with granulocyte macrophage cell stimulating factor (GM-CSF) which converts the dendritic cells from their dormant state into an activated form. Fourth, the activated dendritic cells are infused back into the patient’s blood. Fifth, once back in the body, the activated dendritic cells recruit the killer cells of the immune system, the T-cells, to attack the cancer cells, which are identified by having PAP on their surface.
This five-step process, called “Provenge,” is an elegant and clever way to enhance immune function. Two prospective, double-blind, placebo-controlled trials have proved the efficacy of Provenge. However, one cannot help but wonder why—since Provenge is simply an enhancement of the immune system’s normal function—is all this artificial stimulation in the lab necessary? Why aren’t the dendritic cells in the cancer patient’s immune system detecting the cancer cells spontaneously and recruiting T-cells to attack it?
Another breakthrough has been the discovery that a normally functioning immune system, like all the systems in our body, is tightly organized by a variety of controlling hormones. Obviously, both underactivity and over activity of any system, be it the heart, the pancreas or the immune system, can be dangerous. Now, new research reveals that malignant cells actually manufacture and release excess amounts of controlling hormones that trick the immune system into remaining dormant. Thus the natural process of immune system detection is directly inhibited by the cancer.
Provenge partially circumvents this problem by activating the dendritic cells outside the body in the lab. But the dendritic cells still face a hostile inhibitory environment after they are re-infused. The question arises, “Wouldn’t Provenge work even better if the immune environment in the cancer patient could be rendered more “friendly"?”
In this era of rapid technological advancement it is not surprising that amedicine designed for this specific purpose is already on the market! Yervoy, a monoclonal antibody from Bristol-Myers Squib, was FDA approved to treat malignant melanoma in 2011. Yervoy enhances immune function by counteracting the excess amounts of suppressive hormones being released by the cancer. I heard one researcher characterize Yervoy as the most powerful method available for “taking the brakes off” the immune system.
Provenge and Yervoy used together are so attractive conceptually that the only question remaining is about the optimal method of delivery. Yervoy, unlike Provenge, can have serious side effects. In excess amounts it can induce the immune system to run wild and start attacking the organs in the body like the liver, thyroid and intestines. Caution dictates beginning with a small initial dosage of Yervoy.
In the study we will be conducting at Prostate Oncology Specialists in Marina del Rey the first three patients we treat will be given one-twelfth of a normal dose of Yervoy one week after the Provenge is completed. The second group of three patients will receive a one-sixth dose of Yervoy. The third group of three patients will get three-twelfths of a Yervoy dose. All patients will receive full-dose Provenge and will be closely monitored for disease response, immune function and for possible side effects.
Provenge and Yervoy are just two of the many exciting new methods being studied for harnessing the immune system to fight cancer. However, to my knowledge, we at Prostate Oncology Specialists are privileged to be the first to test the effectiveness of these two exciting treatments in combination. Our first patient is scheduled to start on trial this month.