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 Ouyang1
*Nanjing Galaxy Biopharmaceutical Co. Ltd., Nanjing, China
OX40, a member of the TNF superfamily, is now at the forefront of the field known as “T cell co-stimulation”. It serves as a secondary co-stimulatory immune checkpoint molecule on activated effector T cells and regulatory T cells.
Currently, OX40 agonistic antibodies are being assessed in Phase I/II clinical trials (either as single agents or combination regimens), showing promising antitumor immunity and improved tumor-free survival, which has also been shown preclinically for surrogate anti-OX40 mAbs and OX40L-Fc fusion proteins.
However, we are currently lacking reliable preclinical models for the in vivo assessment of human specific OX40 antibodies. To meet this need, CrownBio has 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.
- The efficacy testing of several human OX40 agonistic antibodies in heterozygous or homozygous KI mice, with promising TGI efficacy as single agents, and much enhanced tumor killing when combined with an mPD-1 antibody.
- That TIL analyses show significantly increased tumor infiltrating T cells & NK cells, correlating with efficacy.