AACR 2023

Depleting hCCR8 mAb Therapy #1: Characterization of a broad collection of anti-hCCR8 mAbs

We demonstrated that treatment with a depleting anti-mCCR8 mAb was able to translate into robust anti-tumor activity in multiple syngeneic models, with induction of potent and tumor specific long-term immunological memory. Moreover, the wide characterization of our diverse mAb library revealed distinct mAb cellular reactivity profiles, different epitope recognition modes (based on binding to different peptides with different post-translational modifications), subnanomolar antagonist activity, and insurmountable property with regards to CCR8 ligand CCL1.

Depleting anti-hCCR8 mAb Therapy #2: Selection of candidates for the development of innovative depleting anti-CCR8 therapeutic antibodies to control the immunosuppressive tumor microenvironment

Lead mAbs from Domain’s unique anti-hCCR8 collection were successfully humanized to deliver novel
antibodies having improved reactivity for HUT78 vs. chimeric ones. In addition, clear differentiating features were
observed with Domain’s humanized mAbs compared with competitors ones currently in the clinic. Amongst
these features, different epitope recognition and capacity to antagonize CCL1-induced receptor internalization
could represent key advantages. Finally, with the aim at optimizing depleting activities of Domain’s lead mAbs, Fc
variants were evaluated for Fc receptors binding and ADCC/ADCP activities. This characterization enabled the
identification of best Fc part for the final candidate selection.

Novel biased PAR2 inhibitors with best-in-class properties reduce resistance to both targeted therapy and immunotherapy in oncology models

A novel series of potent and selective PAR2 inhibitors has been developed by Domain Therapeutics. Data showing their unique features and their potency to alleviate the resistance to both targeted therapy and immunotherapy in cancer models are presented.