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.
Program description
Anti-CCR8 antibody
- Discovery
- Candidate
- Preclinical
- Phase I
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.
In a benchmarking approach, we show that candidate-stage program for the CCR8 target performs better than other CCR8 programs based on a series of assays.
Additional resources
Due to its high and relatively specific expression on tumor-infiltrating Tregs, CCR8 represents an attractive novel target to derive novel immunotherapies.
- At Domain, we successfully discovered and patent-protected a mAb library of several dozen of antibodies with distinct and differentiated binding and activity profiles.
- This collection constitutes a unique source for the development of a best-in-class well-differentiated anti- hCCR8 depleting antibody for the treatment of cancers.
- Based on promising profiles, a set of anti-CCR8 mAb leads with distinct characteristics have entered late optimization phase (humanization, enhanced cytotoxic activity (i.e., ADCC, CDC, ADCP), …). Cell line generation will be initiated in Q1-2023.