Immunotherapies that release the brakes tumours place on the immune system, notably PD-1 and PD-L1 inhibitors, have transformed oncology, yet many patients never respond and others stop responding over time. A study published in Nature by a team led by André Veillette, medical professor at Université de Montréal and researcher at the Montreal Clinical Research Institute, identifies a different kind of brake that may explain part of the problem: SLAMF6, a molecule on the surface of immune cells.
Unlike the better-known checkpoints, SLAMF6 does not need to engage tumour cells to weaken the immune response. It activates itself on the T cell surface, sending a signal that dampens attack capacity, curbs the production of durable T cells and accelerates exhaustion, the state in which T cells simply stop working against cancer. That self-triggering property makes it an unusually insidious suppressor, and a distinctive drug target.
The team developed monoclonal antibodies that prevent SLAMF6 from interacting with itself. In laboratory work these antibodies increased the activation of human T cells, produced more resilient immune cells, reduced the number of exhausted ones and generated strong anti-tumour responses in mice. The researchers, supported by CIHR, the Terry Fox Research Institute and BioCanRx among others, now aim for early-phase clinical trials in solid tumours and blood cancers, with particular promise for patients whose checkpoint therapies have stopped working.