Doctors are hacking a signaling pathway called PD-1 to defeat multiple forms of cancer.
The Food and Drug Administration’s recent approval of pembrolizumab (Keytruda) to treat melanoma was a big deal, not just because melanoma is a hard-to-beat cancer, but also because other cancers share the same features that Keytruda attacks.
One of those cancers is Hodgkin lymphoma. This weekend, researchers published findings that a similar experimental drug, nivolumab, brought about a full remission in almost 90 percent of patients with Hodgkin lymphoma. The 23 patients in the study had not responded well to other treatments, but many of them have continued to thrive a year after they were treated with nivolumab.
Four patients saw their tumors eliminated and 16 saw their tumors shrink by more than half. Six months after receiving the drug, 86 percent of the patients were alive and continued to respond to the drug.
In an editorial note published alongside the study, the NEJM editors call the results “a remarkably high objective response rate.”
“This is a treatment that, rather than targeting cancer cells themselves, targets the immune response, reactivating the T-cells in the neighborhood of the tumor cells,” said Dr. Margaret Shipp, one of the study’s authors, in a press release
Using the body’s own immune system to fight cancer is good for two reasons. First, the immune system is very powerful. Second, immunotherapies like nivolumab also generally result in fewer side effects for patients.
“The immediate clinical effects of the results … are clear and are particularly exciting in suggesting a future in which anti–PD-1 therapy will become the foundation for the treatment of Hodgkin lymphoma, possibly sparing patients both short- and long-term toxic effects of combination chemotherapy,” the NEJM editors wrote.
Nivolumab, like Keytruda, scrambles cancer’s deceptive message — sent along the so-called PD-1 pathway — that tells the immune system it is a friend, not a foe.
To keep the body from over-reacting to minor threats, the immune system features a series of traffic signals. A red light tells the system to ease off, and a green light flags more immune responders through.
PD-1, a protein on the surface of immune T-cells, is one of these traffic signals. Cancer cells have developed ways to turn on the red light, stopping the immune system’s response.
Nivolumab robs cancer of this trick. It blocks the message sent by small molecules called ligands, which are abundant in Hodgkin lymphoma.