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SITC20 Poster 647: Humanized CD137 Knock-In Mouse Model to Assess Chimeric Urelumab

Evaluation of Efficacy and Toxicity of CD137 Immunotherapy with Urelumab-mIgG1 Chimeric Antibody in CD137 HuGEMM™

Hongjuan Zhang, Daniel X. He, Xinhe Feng, Mingkun Zhang*, Annie X. An, Cunxiang Ju*, Chen Jiang, Xiaolong Tu, Henry Q. X. Li, Davy X. Ouyang
*GemPharmatech
SITC20 Poster 647: Humanized CD137 Knock-In Mouse Model to Assess Chimeric Urelumab
CD137 is an attractive immuno-oncology therapeutic target with multiple agonistic antibodies already in clinical testing. Clinical trials are hampered, however, by dose-limiting off-target liver toxicity with treatments using antagonistic monoclonal antibodies therapies like urelumab and utomilumab.

Developing approaches to uncouple liver toxicity from efficacy is also limited by a lack of preclinical models which can be used to assess both the efficacy and immune-related adverse events (irAE) of human CD137 agonistic antibodies. In this poster we discuss the application of a humanized CD137 knock-in mouse to assess urelumab and a range of chimeric modifications.

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  • How a humanized CD137 knock-in mouse model is used to assess human specific CD137 agonistic antibodies

  • That the clinically observed liver toxicity associated with tumor growth inhibition by urelumab is recapitulated using a chimeric version of the antibody in a humanized CD137 knock-in mouse model

  • The importance of both CD137 agonistic antibody version and mouse model in the evaluation of efficacy and irAE

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