ENA21 Poster 003

In vitro and In vivo Characterization of CCR8 Humanized Mouse Model (HuGEMM™)

Daniel X. He1, Keyi Zhu¹, Ruilin Sun², Lei Zheng¹, Annie X. An¹, Henry Q.X. Li^1
1Crown Bioscience Inc., 16550 West Bernardo Drive, Building 5, Suite 525, San Diego, CA 92127, USA; ²Shanghai Model Organisms Center, Inc., 3577 Jinke Rd, Shanghai, 201203 China

CCR8 is a C-C chemokine receptor with seven transmembrane regions, which belongs to the G-protein coupled receptor family. Recently, tumor-infiltrating CCR8+ CD4+ Foxp3+ regulatory T (Treg) cells have been identified as a major immune-suppressive subset in the tumor microenvironment (TME), with CCR8 upregulated in tumor-infiltrating Tregs in patients with breast, lung and colorectal cancer. Among the tumor-infiltrating Treg cells, only 8%-10% of Tregs are CCR8 positive, which are regarded as the master driver populations for Treg-mediated immunosuppression. Thus, CCR8 is increasingly believed to be a potential therapeutic target with monoclonal antibodies specific to human CCR8 (hCCR8) inducing depletion of tumor-resident CCR8+ Treg cells, reverse immunosuppressive signals to enhance the anti-tumor role of effector T cells, particularly in combination with other immune checkpoint inhibitors.

Given the lack of cross-binding to mouse targets of human-specific antibodies, we developed a hCCR8 knock-in mouse model (CCR8 HuGEMM) to evaluate the in vivo therapeutic efficacy of hCCR8 antibodies.

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• The immune components or immune cell subsets development are proportionally normal in CCR8 HuGEMM mice
  
  
• A therapeutic anti-hCCR8 can bind to the T cells (CD8+ and CD4+) from CCR8 HuGEMM
  
  
• A decrease in MDSC(CD3-CD11b+Ly6Chi) populations in blood was observed in non-tumor-bearing CCR8 HuGEMM mice upon therapeutic anti-hCCR8 treatment

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