Abstract 1709: Enhanced proliferation and effector functions of human immune cells in response to immune checkpoint therapy of MDA-MB-231 tumor bearing huNOG mice engrafted with human CD34+ cells

Abstract

Abstract Given the recent success of cancer immunotherapies, well characterized pre-clinical models are needed to enable drug discovery efforts. The recently developed humanized mouse models composed of various types of immune cells offer a unique tool to evaluate aspects of the human immune system in response to immunotherapy. MDA-MB231 cells express high levels of the T-inhibitory molecule PD-L1 making this breast cancer line an ideal candidate for testing the efficacy of the immune-checkpoint inhibitors pembrolizumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in the CD34+ huNOG humanized mouse strain. We analyzed the distribution of CD4 and CD8 T lymphocytes, Treg cells, NK cells and B cells in blood, spleen and tumor samples from MDA-MB231 tumor bearing huNOG humanized treated-mice via flow cytometry. We found that combination therapy enhanced the effector functions of CD4+ and CD8+ T cells associated with increased expression of IFN-gamma and Granzyme B. Supporting this data, we observed an increase in Ki-67+ cells which correlates with a decrease in PD-1 expression in response to pembrolizumab therapy associated with activation of T lymphocytes. In summary, these results demonstrate the potential of humanized mouse models to evaluate the anti-tumor activity of human immune cells in a preclinical setting in response to human specific immune checkpoint targeted therapies. Citation Format: Thi Bui, Karyn McArtan Shinn, Emily G. O'Koren, Ashleigh Derrick, Beverly Godfrey, Ian Belle, Jason Davis, Aidan Synnott, Anya Avrutskaya, Paula L. Miliani De Marval. Enhanced proliferation and effector functions of human immune cells in response to immune checkpoint therapy of MDA-MB-231 tumor bearing huNOG mice engrafted with human CD34+ cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1709.