CCR8 is a type of chemokine receptor that belongs to the C-C subfamily and is a G protein-coupled receptor with seven transmembrane domains. This receptor is mainly expressed in monocytes, Th2 cells, and Treg cells, and it plays a critical role in the development of autoimmune diseases and tumors. The primary ligand for CCR8 in humans is CCL1, which binds to the extracellular loop 2 (ECL2) and the N-terminal domain of the receptor.
In the context of tumors, CCR8 is highly expressed in Treg cells that infiltrate tumors compared to Tregs found in other tissues or peripheral regions of tumors. Thus, CCR8 serves as a valuable biomarker for identifying Tregs within the tumor microenvironment. Targeting CCR8 with anti-CCR8 antibodies can selectively eliminate Treg cells and alleviate the immunosuppression they cause in the tumor microenvironment. Therefore, CCR8 is a promising target for tumor immunotherapy.
Biocytogen and LiberoThera have formed a close collaboration to develop fully human therapeutic antibodies against CCR8 since February 1, 2021. Biocytogen's advanced RenMab® fully humanized transgenic mouse antibody discovery platform, CCR8 target knockout strategy, and LiberoThera's exceptional antigen preparation technology are the basis of this partnership. LiberoThera is responsible for antigen preparation and in vitro antibody screening using a unique GPCR antigen preparation platform, while Biocytogen employs its RenMab® mouse platform for GPCR antibody discovery, leads in vitro screening, and provides effective preclinical efficacy evaluation through its independently developed CCR8 humanized mice.
Through this collaborative development, the parties have identified multiple fully human therapeutic antibody clones with excellent anti-tumor activity in vitro and in vivo, with the potential to become best-in-class products. These clones have high affinity for human CCR8, exhibit cross-species binding, and have a simple manufacturing process. The clones work by depleting Tregs in the tumor microenvironment through enhancing the ADCC effect or inhibiting Treg activity in the tumor microenvironment by blocking the CCR8 signaling pathway mediated by their ligand CCL1. This leads to enhancing the anti-tumor immune response.
July 21, 2022 | Biocytogen and LiberoThera Achieve Milestone Progress in Co-Development of Fully Human GPCR Antibody Drugs