Poster: Humanized OX40 Mouse Models for Preclinical I/O Studies

Preclinical Efficacy Evaluation of Agonistic OX40 Human-Specific Therapeutic Antibodies in a Human OX40 Knock-In Mouse Model (HuGEMM™)

Xuesong Huang, Lei Zheng, Mingkun Zhang*, Annie Xiaoyu An, Jing Zhao*, Xiang Gao*, Jean-Pierre Wery, Qian Shi, and Davy Xuesong Ouyang

*Nanjing Galaxy Biopharmaceutical Co. Ltd., Nanjing, China

OX40 is a co-stimulatory receptor of the TNF receptor superfamily, and is at the forefront of the “T cell co-stimulation” field. While not constitutively expressed on resting, naïve T cells, OX40 instead serves as a secondary co-stimulatory immune checkpoint molecule on activated effector and regulatory T cells.

OX40 agonistic antibodies are already being assessed in the clinic as both single agent and combination regimens. Preclinical evaluation of these agents is, however, hampered by a lack of reliable models to test human origin agents.

To meet this need, CrownBio has developed a humanized drug target knock-in GEMM, where the entire mouse OX40 coding region is replaced with the human counterpart, allowing assessment of OX40 human-specific mAb therapeutics.

Read this Poster to Discover:

  • The efficacy testing of several human OX40 agonistic antibodies in OX40 knock-in mice, with some promising TGI efficacy observed for single agents, which can be enhanced by combination with an mPD-1 antibody.

  • Downstream immunoprofiling of the models, with tumor infiltrating lymphocyte analysis showing significantly increased tumor infiltrating T and NK cells, correlating with efficacy.

  • That the OX40 humanized drug target GEMM provides an urgently needed tool for testing the in vivo efficacy of human OX40 therapeutics, both as single agents and in combination strategies with other treatment modalities.

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