AACR 2023 Poster 29

Characterization of a Murine Intestinal Cancer Homograft Model for Therapeutic Evaluation

Jinxi Wang¹, Leilei Chen¹, Likun Zhang¹, Annie An¹, Ruilin Sun², Jingqian Zhu¹, Lei Zheng¹, Jiajia Zhu¹, Ludovic Bourre¹, Jessie J.J. Wang<sup>1

1</sup>Crown Bioscience Inc., 16550 West Bernardo Drive, Building 5, Suite 525, San Diego, CA 92127
²Shanghai Model Organisms Center, Inc. (SMOC)

Gastrointestinal tract cancers are responsible for over one quarter of the cancer incidence (26%) and over one third (35%) of all cancer-related deaths. Therefore, the development of clinically relevant animal models recapitulating key molecular mechanisms and pathophysiological features is needed. Genetically engineered mouse models (GEMMs) with dysfunctional DNA mismatch repair (MMR) genes, like MLH1 and MSH2, manifest intestinal tumors related to microsatellite instability (MSI). In this study, a murine intestinal cancer homograft from GEMMs with MMR deficiency is established to enroll larger cohorts of mice in a synchronized manner for preclinical studies.

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• Methods for generating MLH1-KO mouse using CRISPR/Cas9 engineering
  
  
• Tumor development in MLH1-KO GEMM mice and characterization of an intestinal tumor homograft, mCR9105
  
  
• In Vivo efficacy results of model mCR9105

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