Abstract 1665: Humanized mice for preclinical efficacy evaluation of drugs targeting CD73

Abstract

Abstract CD73 expressed in Treg surface facilities the hydrolysis of AMP into adenosine which inhibits the activation, expansion and homing of T effector cells.Therapeutic efficiency of CD73 mAb had been studied in C57BL/6 and BALB/C mice xenografted with several murine cancer cell lines. However, for human CD73 mAb with no binding to murine CD73, CD73 humanized mouse models are essential for medicinal development.We established CD73 humanized mouse model (hCD73) on C57BL/6 and BALB/c background in which the mCD73 was replaced with hCD73. Similar expression level of hCD73 in peripheral blood was observed compared with mCD73 in wildtype mice. Besides, the proportion of T, B and NK cells in spleen of hCD73 mice were also analogy to that in wildtype mice. After treating with anti-hCD73 antibody, tumor growth was inhibited in our CT-26-hCD73 tumor model.Furthermore, hPD1/hPDL1/hCD73 mouse models were also established on C57BL/6 and BALB/c backgrounds based on hCD73 mice. However, a better anti-tumor effect of anti-CD73 antibody was found on BALB/c-hPD1/hPDL1/hCD73 bearing CT26 than that on B6-hPD1/hPDL1/hCD73 bearing MC38. Besides, Combination of anti-CD73 and anti-PD1 significant elevated anti-tumor effect comparing with anti-CD73 and anti-PD1 mono therapy in BALB/c-hPD1/hPDL1/hCD73 mice bearing CT26-hPDL1hCD73.In conclusion, BALB/c-hPD1/hPDL1/hCD73 is a well efficient mouse model for therapeutic effect study of anti-CD73 and relevant combination therapy. Citation Format: Xing Liu, Cunxiang Ju, Hongyan Sun, Jing Zhao, Xiang Gao, Zhiying Li. Humanized mice for preclinical efficacy evaluation of drugs targeting CD73 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1665.