Despite the unprecedented success of immune checkpoint blockade therapy in patients with various cancer types, a lack of effective preclinical mouse models remains a major challenge for the development of novel immunotherapeutics. Different strategies to humanize immunodeficient mouse model systems have been reported, including replenishment with human hematopoietic stem cells (HSC) or human PBMC, as well as the development of chimeric models harboring human immune checkpoint targets in immunocompetent mice. CrownBio has successfully established a number of human PBMC-humanized xenograft models known as MiXeno for in vivo immunotherapy evaluation. Our MiXeno platform is a rapid and simple strategy for model humanization. However, aspects such as the optimal PBMC injection route and cell number, the PBMC donor dependence and specificity, and the impact of donor HLA type on the engraftment of immune or tumor cells, etc., require fine tuning. After comparative studies for cell titration and immune cell reconstitution, the optimal inoculation conditions and protocols were established for each model. Immune cell constitution and tumor cell engraftment were synchronized so that graft versus host disease (GvHD) can be managed. Models were also characterized by immunophenotyping. MiXeno is proven as a valid alternative to other humanized mouse models, and has a broad spectrum of applications in immuno-oncology including the evaluation of human specific immuno-modulatory drugs in vivo.
Citation Format: Lan Zhang, Juan Zhang, Meng Qiao, Xuefei Yan, Jian Ding, Fei Chen, Xiaoyu An, WenQing Yang, Qian Shi. Validation and characterization of MiXeno humanized mouse models for immuno-oncology [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B28.