Abstract 1063: In vivo humanized immuno-oncologymodels for drug discovery

Abstract

Abstract Reliable translational, especially humanized mouse models are critical to evaluate efficacy of immuno-therapeutics. While transgenic humanized mice and human CD34+ HSC-reconstituted mice are often used, their human cellular or molecular immune components are limited or defective. Human peripheral blood monocytic cell (PBMC)-reconstitution in immunocompromised mice, although, is transient and limited in infiltrating xenografts, one can manipulate to delicately reconstitute tumor microenvironment with one type, human T cells, or a few types of human immune cells, dendritic and macrophages, from human PBMC, through either systemic reconstitution or local reconstitution. We found that optimized stable PBMC models, both CDX and PDX, can often meet needs of targeting by many developing IO antibody therapeutics, including bi-specifics, in comparison to other humanized models. In particular, for efficacy study and for the convenience of mouse trials, we arrayed panels of PDX models expressing PD-L1 at different levels, in lung, liver, endometrial and gastric cancers, and panels of MSI-H and/or dMMR positive PDX models in these cancer types. In aiding studies of efficacy and resistance, we establish clinically drug-resistant PDX models, such as those resistant to checkpoint antibody drugs. These models are valuable to evaluate efficacy not only for antibody agents but also for combinational therapies involving biotherapeutics such as oncolytic virus. Citation Format: Jijun Cheng, Feifei Zhang, Yuan Long, Wenhua Xu, Hongkui Chen, Danyi Wen. In vivo humanized immuno-oncologymodels for drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1063.