See the end of this post for information about additional trials that are using Ipilimumab and currently recruiting men with hormone refractory prostate cancer.
A multi-site PHASE I study with 33 men has found that a drug called Ipilimumab, also known as MDX-010, has been shown to be able to stimulate the body’s own immune system to fight prostate cancer. The drug, Ipilimumab, was found to be effective in study participants where the tumor has spread and become resistant to hormonal treatment (hormone resistant) and, in some cases, also to chemotherapy.
Tomasz Beer, M.D., a member of the OHSU Cancer Institute, gave an oral presentation on this research Monday, June 2, during the annual American Society of Clinical Oncology in Chicago.
“From what we have seen, this shows that the immune system can be useful to treat prostate cancer. Results show that in some patients, the immune system can be successfully harnessed to cause cancer regressions, and that is both exciting and encouraging,” said Beer, the Grover C. Bagby Endowed Chair for Cancer Research, director of the Prostate Cancer Research Program at the OHSU Cancer Institute, associate professor of medicine (hematology/medical oncology), OHSU School of Medicine.
Seven or 21 percent, of the 33 study participants had PSA declines of 50 percent. This was in a population of men who are nearing the end of having treatments available to deal with their advanced prostate cancer.
Ipilimumab works by blocking a complex set of interactions in the immune system. The immune system is designed to attack foreign invaders such as viruses and bacteria. The immune system creates T-cells to destroy foreign objects through the development of inflammation or by directly killing the objects.
Additionally, the immune system should play a role in surveillance of the body by detecting and eliminating altered cells in the body, such as cancer cells. Whether a cancer progresses or not depends, in part, on the ability of the cancer to evade the immune response.
Many researchers believe that one way in which cancer cells evade the detection of the immune system is by dialing down, or down regulating, the strength of the response of the immune system thus allowing the tumor to grow.
An important mechanism for the down regulation of the immune system is the molecule called CTLA-4. Normally, the T cells are activated by other immune cells which are called dendritic cells. The dendritic cells literally lable the foreign, or cancerous cells as antigens and direct the T cells to be active against them. However, after this initial activation, CTLA-4 appears on the surface of the T cells. When CTLA-4 interacts with the dendritic cells, the next set of signals given to the T cells is to turn the immune response down, or even off.
CTLA-4 is part of the normal regulatory mechanism that is designed to protect the body from immune system overreactions. When CTLA-4 is expressed in the presence of mutant cancer cells, the system is down regulated and the result is eventual tumor evasion and cancer progression. Ipilimumab is an antibody that blocks the signaling of CTLA-4, allowing the immune response to have a stronger anti-tumor effect by inhibiting the down regulation of the T cells.
There are currently four active (recruiting) clinical trials in the United States evaluating Ipilimumab for advanced prostate cancer treatment. You can get additional information on these rials at: Ipilimumab Trials.
You can learn more about cancer vaccines from the many posts I have written about Provenge. Just go up to the search bar on the upper right of this blog and search for Provenge and vaccines.
Joel T Nowak MA, MSW