CCR8 (chemokine receptor 8 ) is highly expressed on the surface of certain regulatory T cells (Tregs).
Tregs are a specialized population of T cells that inhibit other immune cells. In tumors, Tregs prevent the body’s immune system from fighting the cancer. Thus, Treg cells are a barrier to cancer treatments.
Tregs often express high levels of CCR8 when they are associated with solid tumors. Other Tregs throughout the body express CCR8 at very low levels or not at all. This restricted expression pattern makes CCR8 an excellent target for therapeutics.
In tumors, CCR8-expressing Treg cells inhibit other immune cells, shutting down immune responses against cancer cells. Thus, CCR8 is an important immuno-oncology target.
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Therapeutic Potential: Antibodies targeting CCR8 for immuno-oncology
A therapeutic antibody that binds CCR8 could find and kill tumor-associated Tregs, opening the door to cancer-fighting cells and other therapies. MAbs targeting CCR8 could be used either as a monotherapy or as part of a combination therapy.
Using our proprietary MPS Antibody Discovery platform, we generated a large, diverse panel of humanized CCR8 MAbs. Screening and validation yielded 12 unique molecules with nanomolar and sub-nanomolar affinity.
Removing CCR8-positive Tregs could allow other immune cells to move into the tumor and kill cancer cells.
The Opportunity: High-affinity, humanized CCR8 MAb candidate panel
We have a panel of six CCR8 MAbs ready for evaluation and preclinical development as an immuno-oncology therapeutic. Because they are cross-reactive with CCR8 in mice and other species, these MAbs are suitable for studies using easily accessible animal models.
We have preliminary data showing antibody-drug conjugate (ADC)-mediated cell killing. We are exploring other cytotoxicity mechanisms, including formats for antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).