January 01, 2017
Pierorazio, Allaf, Drake, and Ball: Checkpoint inhibitors can produce amazing results, but they don’t work for everyone. Genetic differences make some tumors easier for the immune system to recognize.
Checkpoint inhibitors are exciting new drugs that help the body’s immune system recognize cancer and attack it. “Tumors are able to turn off the immune system, but checkpoint inhibitors turn the immune system back on,” explains urologist Mark Ball, M.D. These drugs have achieved results considered miraculous in lung cancer, melanoma, and other cancers – in many cases, causing advanced tumors to melt away. They don’t work for everyone, and scientists are working hard to figure out why, so that these people can be helped, too.
“A small number of patients have long-term responses even after the drug is stopped.”
One of these drugs, called Nivolumab, has recently been approved as a treatment for metastatic kidney cancer. “Overall, between 20 to 30 percent of patients have a response to the drug,” says Kimmel Cancer Center scientist Chuck Drake, M.D., Ph.D. “More exciting, however, is that a small number of patients have long-term responses even after the drug is stopped.” Ball, who just completed his Brady residency, recently completed a study of these “exceptional responders,” along with Drake and surgeon-scientist Mohamad Allaf, M.D. They found that patients with exceptional response had more mutations in their tumors – making them easier for the immune system to recognize – plus higher numbers of CD8 T cells, particularly powerful immune cells that fight cancer. In these exceptional responders, too, certain genes were activated: “We found several genes that we did not know were involved in the mechanism of response to this drug,” Drake explains.
“This work may help us find out which patients will respond best to this drug,” says Allaf, and which patients will do better with different forms of treatment. These findings were presented at the Genitourinary Cancer Symposium in San Francisco and the American Urological Association’s annual meeting in San Diego.