Background
FDA has granted Fast Track Designation for SAR’579/IPH6101, a trifunctional anti-CD123 NKp46xCD16 NK cell engager, for the treatment of hematological malignancies. Besides, there are many antibodies, based on NK cell engager therapeutics or antibody-dependent cellular cytotoxicity (ADCC) through CD16A, for cancer treatment in the preclinical and clinical trial.
Methods
FcRs are cell surface receptors that bind to the Fc portion of antibodies, mediating various immune functions such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. The FcR humanized mouse model is designed to express human FcRs on mouse immune cells, allowing researchers to study the interactions between human antibodies and human FcRs in an in vivo system. Gempharmatech developed the FcgRs humanized mouse model, carrying the FcRs encoding genes (FCGR1, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCGR3B) while lacks endogenous murine FcgRs genes (Fcgr1, Fcgr2b, Fcgr3, Fcgr4) in C57BL/6JGpt background.
Results
The mouse model can express human CD16A on NK cells and macrophages, which was consistent with the human. And the human CD32 can also be detected on neutrophils in B6-hFcgRs. As expected, the growth of subcutaneously engrafted MC38-TAA cells tumor in B6-hFcgRs mice, was strongly inhibited by the mAb-mediated ADCC effect against.
Conclusions
In conclusion, These FcR humanized mouse models enable researchers to investigate the interactions between human antibodies and human FcRs in a physiological context. They have been utilized to study antibody therapies, immune cell-mediated cytotoxicity, and the efficacy and safety of therapeutic antibodies. These models provide valuable insights into FcR biology and help guide the development of immunotherapies targeting FcR-mediated pathways in human diseases.