Therapeutic antibodies for tumor-associated Treg cell depletion

The Target: CCR8 on immune-suppressing Treg cells

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.

A tumor with associated Treg cells, showing seven-transmembrane-domain CCR8 in the cell membrane. The Tregs are blocking the activity of an effector T cell and an antigen-presenting cell.
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.

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.

A tumor with no Treg cells is being infiltrated by other immune cells.
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).

For more about CCR8 as an oncology target, see Haruna et al., 2022.

For more assets available to license, visit our Therapeutic Pipeline page

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