Most immune brakes need a tumor to push them. This one pushes itself.
The molecule is SLAMF6, and it sits on the surface of T cells, the immune cells that go after cancer. A team led by Dr. André Veillette, a medical professor at the Université de Montréal and director of the Molecular Oncology Research Unit at the Montreal Clinical Research Institute (IRCM), found that SLAMF6 can switch itself on directly at the T cell surface. They published the work in Nature.
How it works
Known immune checkpoints generally have to interact with tumor cells before they weaken the body’s defenses. SLAMF6 skips that step. When it binds to itself, it sends signals that cut the ability of T cells to attack cancer, reduce the number of strong, long-lasting T cells, and speed up exhaustion, the state in which T cells stop working against a tumor.
That matters because of how today’s drugs operate. PD1 and PDL1 inhibitors remove inhibitory signals created by tumors. They have helped many patients, but a significant number do not respond, or respond for a while and then develop resistance. A brake that works without the tumor’s help would sit outside the reach of those drugs.
An antibody to jam it
Veillette and his colleagues built monoclonal antibodies meant to stop SLAMF6 from binding to itself and triggering its suppressive signals. In laboratory tests, the antibodies produced larger numbers of durable immune cells. The researchers say they perform significantly better than any earlier approach aimed at SLAMF6. Work in mice showed the cells staying stronger and attacking tumors more effectively.
The team thinks the antibodies could anchor a new class of cancer immunotherapies, possibly for patients who no longer benefit from PD1 or PDL1 treatment. They might be given alone or alongside other drugs that stimulate the immune system. Early-stage clinical trials in people with solid tumors and blood cancers are the next step. Nothing has been tested in patients yet.
“The discovery made by Dr. Veillette’s team opens the door to a new chapter in immunotherapy,” said Dr. Jean-François Côté, IRCM’s president and scientific director. He described SLAMF6 as “an internal brake that had until now gone unrecognized.”
The study, titled “SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer,” was funded by the Canadian Institutes of Health Research, the Terry Fox Research Institute, BioCanRx, Québec’s Ministry of Economy, Innovation and Energy, and the Canadian Foundation for Innovation.
Sources
Sources
- Unraveling the mystery of why some cancer… – UdeMnouvelles
- The secret reason some cancer treatments stop working | ScienceDaily
