Abstract 2833: Validating cancer biomarker expression on mouse cell-derived xenograft models of human cancer

Abstract

Abstract Background and Objective: The target antigen expression level is critical for the potency of immune therapies like ADC, mRNA-LNP, and CAR-T. Selecting an appropriate cancer model remains a challenge to the pre-clinical drug testing. HD Biosciences offers over 1000 cell lines and 150 CDX mouse models of human cancers. Furthermore, we have validated the expression of three therapeutic targets Nectin-4, Trop2, and PD-L1 in various CDX tumor tissues. This poster will highlight some recently established models as well as the antigen validation result. Our study provides a reference that guides the model selection of efficacy studies targeting Nectin-4, Trop2, or PD-L1. In addition, we offer a platform to validate the expression of target antigens in CDX mouse models covering numerous cancer types. Method and Result: Biomarker surface expression of Nectin-4, Trop2, and PD-L1 on xenograft tumors was validated by IHC staining and FACS analysis. We highlight these models with high expression of each marker. These models are available to support further efficacy studies of anti-cancer drugs targeting the marker. We also analyzed the biomarker surface expression in vitro using cell pellets via FACS analysis to compare with the in vivo expression level. Hence, the biomarker gene expression level was confirmed by FACS. Interestingly, the result indicates biomarker expression in mouse tumor tissues is often inconsistent with in vitro cell expression. For example, the A375 CDX model on humanized immunodeficient mice is commonly used for anti-PD-1/PD-L1 drug efficacy tests. However, the surface expression of PD-L1 is only detected in the A375 tumor tissues and is undetectable in the A375 cell pellet. This finding could explain the inconsistency of in vitro and in vivo drug test results. The in vivo CDX model-based biomarker would better predict the drug’s efficacy, as the model better mimics the clinical situation of tumor burden in patients. Conclusion: In vitro gene expression and protein expression of cell surface biomarkers may not be relevant to the in vivo tumor surface expression level, resulting in inconsistent efficacy data in vitro and in vivo. Thus, validating targeted biomarkers in vivo is crucial for choosing the best cancer tumor model with high target expression for drug efficacy validation. HD Biosciences provides validated 150 CDX models expressing Nectin-4, Trop2, and PD-L1 and have in vivo capability for target validation and drug efficacy study. Citation Format: Minqi Huang, Alyssa E. Wiggins, D Marroquin, Mengling Liu, Luke Tsai. Validating cancer biomarker expression on mouse cell-derived xenograft models of human cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2833.