Abstract B014: MuScreen allows profiling of antitumor efficacy and biomarker readouts of drug candidates using well-characterized syngeneic models

Abstract

Abstract Introduction: Syngeneic model is a useful tool for evaluating the antitumor effect of cancer immunotherapy. Crownbio’s MuScreen is the first in vivo screening tool to test novel I/O drug candidates utilizing multi-syngeneic models. To better understand interplay between immune-modulation and antitumor phenotype in a dynamic fashion, we performed a series of comprehensive in vivo/ex vivo studies. Capturing dynamic change of percentage of tumor-infiltrated lymphocytes (TIL) of tumor-bearing mice upon treatment with checkpoint inhibitors, and establishing correlation between in vivo efficacy and TIL changes can not only shed light on MOA of I/O drugs but also provide critical information on data interpretation and model selection. Methods: Leveraging in-house detailed profiling data on our syngeneic models, including benchmarking efficacy data, tumor RNA-seq data, and comprehensive immune-FACS analysis, CrownBio has launched a new service platform: MuScreen. MuScreen includes up to 20 well-characterized syngeneic models in a 3-month screening run. Both PD and efficacy may be determined in the screen, allowing researchers to make decisions based on results observed from a large dataset. MuScreen offers a cost-effective feature where test agents from multiple clients can be pooled together for each run (sharing vehicle and other common groups), providing a significant reduction in the number of animals used and the associated costs. A comprehensive and large scale PD-efficacy correlation study was conducted in which a panel of syngeneic tumor models was treated with efficacious doses of anti-PD1 mAb. Tumor-bearing mice were monitored for both antitumor activity and PD marker modulation at designated time points by using FACs or IHC Results: MuScreen offers a large-scale murine syngeneic-based platformthat allows evaluation of test articles systemically using 12-20 well-characterized mouse tumor models. Both BD marker modulation and efficacy can be determined. The MuScreen models were further characterized and validated using checkpoint inhibitors in order to link immune-modulation and antitumor activity. Correlational analysis was performed to reveal dynamic relationship between immune-profiling changes and antitumor effects. Conclusions: MuScreen represents a powerful screening platform for I/O drug evaluation using a collection of well-characterized syngeneic tumor models. The data set from a large-scale validation study using 12 syngeneic models reveals dynamic changes of both immune-profiling and antitumor response, which may be critical for model selection and data interpretation. Citation Format: Ying Jin, Lan Zhang, Binchen Mao, Guoqin Zhai, Zhongliang Li, Meng Qiao, Xiaoyu An, Juan Zhang, Sheng Guo, Qian Shi, WenQing Yang. MuScreen allows profiling of antitumor efficacy and biomarker readouts of drug candidates using well-characterized syngeneic models [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B014.