Recently approved cancer immunotherapy drugs have been shown to not only suppress tumor growth but also prolong survival of patients with various tumor types. More and more relevant and sophisticated preclinical tumor models are required by the I/O drug discovery industry. Different strategies of humanized mouse model systems have been published, including human hematopoietic stem cell (HSC) humanized and human PBMC reconstituted tumor models; each has advantages and disadvantages. Compared with HSC humanization, using human PBMC cells to reconstitute human immune system demonstrated fast engraftment and less variable results. CrownBio has successfully established a platform, known as MiXenoTM,that uses PBMC-humanized xenograft models to evaluate the in vivo antitumor activity of immunotherapeutics of human origin. The platform has proven to be a valuable tool and is being widely used by our collaborators. The current study is designed to address model optimization and application aspects of the MiXeno platform, including PBMC donor to donor variation, feasibility of in vitro PBMC donor screening, and selection of suitable models for different targets. More than a dozen MiXeno tumor models have been established and validated where human immune cells were reconstituted in the mouse system for evaluation of human-origin bispecific antibodies, immune checkpoint inhibitors, or immune modulators. These MiXeno models were characterized with regards to reconstitution of T cells, tumor response to anti-PD-1 and anti-CTLA4 antibodies, and onset of possible graft-versus-host disease (GVHD) or graft-versus-tumor response (GVT). Evaluation of expanded immune-oncology therapeutics is in progress, including NK and dendritic cells-targeted immune-modulating drugs.
Citation Format: Lan Zhang, Juan Zhang, Meng Qiao, Xuefei Yan, Jian Ding, Fei Chen, Xiaoyu An, Weibin Tan, Xiaoyan Fu, WenQing Yang, Qian Shi. MiXenoTM: a fast and efficient humanized tumor model system for in vivo efficacy evaluation of novel immunotherapeutics [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 B078.