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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

Treg are one of the most important immunosuppressive immune cell population responsible for the failure of several therapeutic approach in the clinic.

CCR8 is a GPCR target specifically expressed by Tumor infiltrating Treg which make this target highly strategic to derive efficient novel immunotherapies.

Domain Therapeutics has discovered a unique collection of proprietary anti-hCCR8 antibodies showing clear differentiating factors and demonstrating advantages over the most advanced CCR8 antibodies in the clinic. Domain has nominated a best-in-class candidate, DT-7012 and CMC work is currently on-going. Current expectations are start of Phase I mid-2025.

 

 


Additional resources

Beyond CCR8: key epitopes targeting dynamic CCR8 conformational states and a diversity of monoclonal antibodies to modulate the tumor microenvironment for the treatment of cancers

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.

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