HuGEMM™ OX40 Mouse Model

FATZO Mouse

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HuGEMM™ OX40 Mouse Model Description

The HuGEMM OX40 mouse model is a chimeric tumor model where the mouse immune system is functional and the OX40 receptors have been humanized for a more translational immune response.

The OX40 model was developed by replacing the entire coding region of the mouse receptor with its human counterpart, which allows the receptor to be recognized by the therapeutic antibody of interest. This enables the ability to test the therapeutic efficacy directly in the mouse model.

OX40 plays two roles in immune response by activating and amplifying T-cell response. Engagement of OX40 by ligand or agonistic antibody leads to dramatic expansion, effector function, cytokine production, and survival of T cells.

Benefits of HuGEMM Models

  • Humanized drug targets eliminate and reduce interspecific (species) effects of the compound providing a platform to evaluate therapeutic antibodies which are not cross-reactive to the mouse protein

  • Enables the evaluation of specific human biological therapies in vivo

  • Provides an efficient method to study a range of targets for human immunotherapies

OX40 Model Characterization Data

Figure 1: Expression of human and mouse T cells across WT, heterozygous KI, and homozygous KI HuGEMM OX40 models. The WT animal expresses only mouse OX40 on T cells, and the homozygous KI expresses only human OX40 on T cells, while the heterozygous KI expresses both human and murine OX40.

Figure 2: Validation of homozygous HuGEMM OX40 models evaluating anti-mPD1, hOX40, and a combination of mPD1 and hOX40 antibodies. Graph 1 shows no meaningful tumor growth inhibition (TGI) following treatment with anti-hOX40, graph 2 shows 47% TGI for hOX40 and graph 3 shows 43% TGI for hOX40.

Figure 3: HuGEMM OX40 heterozygous efficacy assessment evaluating anti-mPD1, hOX40 (MOXR0916 analog), and a combination of mPD1 and hOX40 antibodies. Graph 1 shows the mean TGI of each group and reflects 41% TGI for mPD1, 49% TGI for hOX40, and 91% TGI for the combination of mPD-1and hOX40 antibodies. Graph 2 shows the individual spider plots for each group in the study and shows 4 out of 8 mice in the combination group were cured.