SLAMF6 discovery offers hope for non-responding cancer patients

Cancer researchers working on immunotherapies have made a big discovery: SLAMF6, a molecule on the surface of immune cells that prevents T cells from effectively attacking tumors – and, in mice, they've found a way to neutralize it. 

Led by Université de Montréal medical professor Dr. André Veillette, director of the molecular oncology research unit at the UdeM-affiliated Montreal Clinical Research Institute (IRCM), the breakthrough is detailed in a study published in Nature.

An internal brake independent of tumor cells

In their lab, Veillette and his team demonstrated that, unlike other inhibitory molecules, SLAMF6 does not need to interact with tumour to weaken the immune response. It self-activates directly on the surface of T cells, sending a stop signal that: 

• weakens their attack capacity;
• reduces the production of healthy, robust, long-lasting T cells;
• and accelerates immune exhaustion, a state in which T cells become ineffective against cancer. 

Current immunotherapies, such as PD1 or PDL1 inhibitors, "release the brakes" that tumours impose on the immune system. But a large number of patients either do not respond or eventually stop responding to these treatments.

To counter this effect, Veillette and his co-researchers developed new monoclonal antibodies that prevent SLAMF6 from interacting with itself. These antibodies have shown remarkable effects that include: 

• more activation of human T cells;
• higher numbers of resilient immune cells;
• fewer exhausted T-cells;
• and strong anti-tumour responses in mice. 

Outperform all other approaches

These new antibodies far outperform all currently available tools targeting SLAMF6, making them leading candidates for a new generation of anti-cancer immunotherapies, Veillette and his co-researchers believe.

The antibodies could offer an option for patients who no longer respond to PD1 or PDL1 treatments and could be used either alone or in combination with other immune-stimulating therapies, they say. 

As a next step, Veillette's team now wants to test these antibodies in early-phase clinical trials to evaluate their safety and efficacy in people with solid tumours or blood cancers. 

The discovery made by Dr. Veillette's team opens the door to a new chapter in immunotherapy."

Dr. Jean-François Côté, IRCM president and scientific director 

"By identifying an internal brake that had until now gone unrecognized and by developing antibodies capable of neutralizing it, our researchers are offering an innovative solution to the limitations of current treatments," he said.

"Rooted in a strategic vision to develop precision therapeutics, this breakthrough brings real hope to many patients and stands as a strong example of the impact of the translational research conducted at the IRCM."