As evidenced by strong clinical data from antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death protein-1 (PD-1), and its ligand PD-L1, cancer immunotherapy is now a major breakthrough in cancer treatment. Meanwhile, new immunotherapeutic agents with various targets and mechanisms, as well as new drug combinations are under active preclinical development. However, reliable humanized animal models are of increasing importance as more programs are reaching the in vivo stage, where direct evaluation of therapeutics with anti-human targets are necessary. We have previously reported our efforts in generating mouse MiXeno models that harbor human immune cells by engrafting immuno-deficient mice with human PBMC (the MiXenoTM model) to evaluate anti-PD-L1 antibody. In the current study, we carried out extensive validation of these models in vivo by generating multiple cell line-derived MiXeno models and testing them with anti-human PD-1 or PD-L1 antibodies in different animal strains (NOD/SCID vs. NPG). Our studies demonstrated that MiXeno models can successfully reconstitute human T cells in mice to support the anti-tumor activity of the immuno-therapeutic agents. MiXeno model is simple and fast, and may become valuable tools for in vivo evaluation of immunotherapeutic agents.

Citation Format: Juan Zhang, Meng Qiao, Lan Zhang, Qian Shi. Validation of anti-human PD1 and PD-L1 antibodies in MiXeno mouse models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3235. doi:10.1158/1538-7445.AM2015-3235

©2015 American Association for Cancer Research.
2015