One of the immunosuppressive mechanisms triggered by some tumors to bypass immune response and responsible of immune checkpoint inhibitor treatment failure, is based on regulatory T cells (Tregs). In the tumor microenvironment (TME), Tregs facilitate self-tolerance by suppressing effector immune function (T and NK cells) through inhibitory cytokines, thereby limiting the antigen-specific immune response. Infiltrated within the tumor, Tregs act as brakes on the anti-tumor immunity. Therefore, targeting Treg receptors specifically overexpressed in the context of cancer constitutes a promising approach in cancer immunotherapy.
Using our cross-validated strategy, Domain identified the C-C motif chemokine receptor 8 (CCR8) as a major target specifically overexpressed in a context of tumors resistant to immune checkpoint inhibitors.
Based on this data and a solid proof of principle package, we have launched and progressed a program aiming at bringing to the clinic a monoclonal antibody targeting CCR8 to deplete tumor infiltrated Tregs and restore immunosurveillance.
The program is currently at the discovery stage.