Abstract
Abstract CD137 (41-BB, tumor necrosis factor receptor superfamily 9), expressed on activated T cells and NK cells, has gained increased attention as an anti-tumor target because of remarkable clinical efficacy using either a single agent or in combination with other immune checkpoint inhibitors. We constructed CD137 humanized mice based on two different backgrounds, C57BL6 and BALB/c mice, as well as dual-target and triple-target mice crossbred with PD1/PDL1 humanized mice to create an ideal model to study CD137 target drugs. The normal immune cell population in peripheral blood were not affected in CD137 humanized mice, and hCD137 was expressed on T cells after the stimulation with a anti CD3 antibody. We verified the efficacy of anti-CD137 drugs in BALB/c-hCD137 mice inoculated with different cancer cell lines (i.e. CT26, EMT6 and 4T1). The drug Urelumab showed a dramatic response in the hCD137 mice model inoculated with CT26 and EMT6 but not with 4T1 cell line. In a rechallenge study, no tumors grew in tumor-free mice previously treated with Urelumab, with effector memory T cells increased in peripheral blood, indicating Urelumab has a relatively long-lasting anti-tumor effect. The combination of Urelumab and anti-PD1 has a stronger tumor growth inhibition effect than that of anti-CD137 or anti-PD1 monotherapy on dual-target or triple target mice. These data show that the humanized CD137 mouse is a suitable model for evaluating the monotherapies or combination therapies targeting CD137. Citation Format: Yunlong Jiang, Tingting Gu, Weiwei Yu, Hongyan Sun, Mingkun Zhang, Juan Liang, Shuai Li, Cunxiang Ju, Jing Zhao, Xiang Gao, Mark W. Moore. CD137 humanized mice for preclinical efficacy evaluation of therapeutic antibodies [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 5623.
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