Poster A207: Evaluate the Efficacy of Human OX40 Therapeutics and Combination Regimens In Vivo

Utilizing Human OX40 Knock-In Mice (HuGEMM™) to Assess the Antitumor Efficacy of OX40 Agonistic Antibodies

Xuesong Huang, Lei Zheng, Wenyi Ouyang, 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 member of the TNF superfamily, and is now at the forefront of the field known as “T cell co-stimulation”. Immune co-stimulators work by providing the signal that promotes the expansion and proliferation of killer CD8 and helper CD4 T cells.

Several OX40 agonistic antibodies are in early stage clinical development, showing promising antitumor immunity and improved tumor-free survival. Preclinical studies using surrogate OX40 antibodies have also shown robust tumor growth inhibition, particularly in combination with checkpoint inhibitors e.g. anti-PD-1 and CTLA-4.

However, we are currently lacking reliable preclinical models for the in vivo assessment of human specific OX40 antibodies. CrownBio has therefore developed a human OX40 knock-in GEMM, with the entire mouse OX40 coding region replaced with the human counterpart. This poster covers the model targeting strategy, validation, and initial efficacy studies including combination with anti-PD-1 antibodies.

Read this Poster to Discover:

• That human OX40 is expressed in both hetero- and homozygous knock-in mice at a higher level compared with wild type C57BL/6 mice
• How some OX40 agonistic antibodies show promising TGI against syngeneic tumors engrafted in this model, with efficacy linked to increased tumor infiltrating T and NK cells
• That this humanized OX40 model provides an urgently needed tool for testing the in vivo efficacy of human OX40 therapeutics, both as single agents, and various combination strategies with other treatment modalities

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