How Do You
Teach the Immune
System to Hate
Immune cells have the potential to attack prostate cancer and kill it very quickly.
Unfortunately,they don’t do that. Why don’t they realize prostate cancer is the enemy?
Charles Drake, second from left, with Tina Ceccato, Chris Nirshl, and Nick Durham,
is working to find out.
Ideally, the body’s immune system would spot prostate cancer, recognize that it’s not supposed to be there, and destroy it. Instead, says immunologist Charles Drake, M.D., Ph.D., The Nancy and Jim O’Neal Scholar, immune cells — which have the potential to be warriors that could attack and kill very quickly — see prostate cancer, and actually recognize it. Then, frustratingly, they seem to say, “Oh, prostate cancer, I thought that was you. How are you doing?” And nothing else happens.
“Unfortunately,” says Drake, “this recognition does not lead to immune attack and eventual rejection of the tumor, as we would hope. One of the most important reasons why this occurs is because immune cells are ‘tolerized,’ or turned off, when they see cancer cells.” This turning off, he adds, is controlled in part by proteins on the surface of immune cells, known as checkpoints.
Then, frustratingly, they seem to say,
“Oh, prostate cancer, I thought that
was you. How are you doing?” And
nothing else happens.
In recent clinical studies of people with kidney, lung, and skin cancer, “our group helped to show that a blockade of the immune checkpoint, controlled by a molecule called PD-1, could lead the body’s immune system to reject tumors. But this therapy does not work in all patients,” says Drake, and this seems to be because a silent partner — another checkpoint protein — is involved. “In the laboratory, we found that many of the immune cells that are not reacting to cancer also express another checkpoint, known as LAG-3. Fascinatingly, we found that blocking both LAG-3 and PD-1 can lead to rejection of tumors that can’t be treated by blocking either one alone. Our hope is to translate these fi ndings to prostate cancer, by treating patients with drugs to block both checkpoints at the same time.”
Other immunotherapy news:
In a review article for Clinical Cancer Research, Drake and James Gulley, a colleague at the National Institutes of Health, recently looked at the progress in therapeutic cancer “vaccines.” One of these drugs, sipuleucel- T (Provenge), has been approved by the Food and Drug Administration as the fi rst therapeutic anti-cancer vaccine. The good news is that over the last few years, scientists have learned a lot about timing — when in the tumor’s growth it is most vulnerable to immunotherapy and more traditional chemotherapy drugs — and combination, adding a vaccine to other immunotherapy drugs, or to different kinds of drugs.
“Very few metastatic cancers are currently treated with just one chemotherapy drug,” says Drake. “Instead, combination chemotherapy can be curative for patients with testicular cancer and other cancers. Thus, it makes sense that combination immunotherapy might also hold clinical promise.” Clinical trials are needed to see whether sequencing immunotherapy and hormonal therapy, or conventional chemotherapy, achieves greater effect in prostate cancer, he adds. “Preclinical data overwhelmingly suggest that combination approaches could lead to major advances in clinical benefit.”