Poster 226: Immune Checkpoint Double Knock-In Models for I/O Testing

Generation of human immune checkpoint double knock-in mice (dKI HuGEMM^™) for preclinical efficacy assessment of combinatorial therapeutic antibodies

Lei Zheng, Daniel X. He, Ruilin Sun*, Annie X. An, Jian Fei”, Henry Q.X. Li, Davy X. Ouyang
*Shanghai Model Organisms Center, Inc., 3577 Jinke Rd, Shanghai, 201203 China

Combinations of immune checkpoint inhibitors (ICIs, e.g. PD-1 and CTLA-4) are being clinically assessed to try and overcome the low response rate seen for single agent use. To allow preclinical ICI combination testing, immunocompetent models are needed which can be used with pairs of human specific ICIs.

We’ve previously reported on our HuGEMM platform of immune checkpoint target humanised mice. Models are available for a variety of single immune checkpoints including PD-1, PD-L1, CTLA-4, OX40 etc for assessing the corresponding human antibody.

This poster details the generation of double knock-in HuGEMM mouse models, featuring human PD-1/PD-L1 and PD-1/CTLA-4 pairs, model validation, and model use in preclinically evaluating combination checkpoint inhibitor regimens.

Read this Poster to Discover:

• That double knock-in immune checkpoint target humanised mice are a robust platform for testing ICI combinations, as well as ICIs plus other anti-tumour therapeutic modalities
  
  
• That PD-1/PD-L1 combination treatment showed slightly improved efficacy compared to the same dose levels of single agents using a double PD-1/PD-L1 knock in model
  
  
• How PD-1/CTLA-4 double knock in model combination treatment showed synergistic effects, with complete tumour remission and resistance to tumour re-challenge

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