In the realm of cancer immunotherapy, natural killer (NK) cells have emerged as a potent force against cancer, capable of destroying even metastatic cells without provoking an immune response against the foreign cells. Eric Vivier, Chief Scientific Officer of Innate Pharma, and his team are pioneering the development of NK cell engagers. These molecules create 'molecular bridges' between immune cells and their targets, leveraging the patient's existing immune cells to combat cancer without the need for additional cell infusions.
A recent study published in Science Immunology demonstrates the efficacy of a four-pronged engager in activating NK cells to fight B cell non-Hodgkin lymphoma in animal models. This approach not only targets cancer cells expressing the CD20 antigen but also those lacking it, a capability beyond the reach of T cells. The engager's design includes targeting the CD20 antigen on B cells and activating NK cells through CD16 and NKp46 receptors, alongside stimulating the IL-2 cytokine receptor to enhance NK cell activity without affecting T cells.
Preliminary results from mouse and non-human primate models are promising, showing effective activation of NK cells, destruction of B cells, and minimal side effects. The engager's ability to achieve high affinity and specificity in NK cell activation, coupled with sustained anti-cancer response through IL-2 receptor signaling, addresses significant challenges in NK cell-directed therapies.
Currently in Phase 1 clinical trials, this NK cell engager represents a potential second-line treatment for lymphoma patients who have relapsed after T cell immunotherapies. The flexibility of the engager platform, capable of targeting various cancer molecules and immune receptors, opens new avenues for treating solid tumors and autoimmunity, traditionally resistant to immunotherapy. Innate Pharma's collaboration with Sanofi and the development of multiple engagers in the clinical trial pipeline underscore the therapeutic potential of this innovative approach.
