Abstract 2562: Evaluate in vivo efficacy of anti-tumor immuno-therapeutics using MixenoTM mouse models

Abstract

Abstract The past few years have witnessed a renaissance in the field of cancer immunotherapy, relating largely to the clinical advances associated with the development of immunomodulatory agents, e.g. monoclonal antibodies targeting the immune inhibitory pathways (CTLA-4 and PD-1/PD-L1). Often, the preclinical efficacy assessments are based on the evaluation of surrogate anti-mouse target antibodies using mouse syngenic tumor models, because of the need for T cell activation in an immune competent system. However, this strategy is limited due to the fact that the immune systems in human and mouse are different, and a surrogate molecule needs to be tested in those syngenic models. Here we set out to validate mouse models that harbor human immune cells by pre-engrafting the immuno-deficient mice with human PBMC (the MixenoTM model), and use them for efficacy evaluation of the humanized anti-PD-1 antibody. PD-L1 high-expression human tumor cell lines are selected for these in vivo models. T cell activation, infiltration and the cytokine production were analyzed to illustrate the immune cell involvement. In conclusion, the MixenoTM models are useful tools in immunotherapeutic antibody development, and may greatly increase the clinical translatability of animal studies. Citation Format: Juan Zhang, Junzhuan Qiu, Ziyong Sun, Xin Dong, Zha Jiping, Qian Shi. Evaluate in vivo efficacy of anti-tumor immuno-therapeutics using MixenoTM mouse models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2562. doi:10.1158/1538-7445.AM2014-2562