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487 A noval mouse model for preclinical efficacy of the antibodies associated with the target CD16A
  1. Xiaoliu Yang,
  2. Huiyi Wang,
  3. Mingkun Zhang,
  4. Wen Zeng,
  5. Cunxiang Ju,
  6. Jing Zhao and
  7. Xiang Gao
  1. GePharmatech Co. Ltd., Nanjing, Jiangsu, China
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background FDA has granted Fast Track Designation for SAR’579/IPH6101, a trifunctional anti-CD123 NKp46×CD16 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 FcγRs 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 FcγR humanized mouse model is designed to express human FcγRs on mouse immune cells, allowing researchers to study the interactions between human antibodies and human FcγRs in an in vivo system. Gempharmatech developed the FcgRs humanized mouse model, carrying the FcγRs 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 FcγR humanized mouse models enable researchers to investigate the interactions between human antibodies and human FcγRs 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 FcγR biology and help guide the development of immunotherapies targeting FcγR-mediated pathways in human diseases.

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