Abstract 1050: Characterization of human cancer cell line xenografts in humanized mice

Abstract

Abstract Studying immune-oncology (IO) agents that target the human immune system in mice have posed challenges for oncology researchers. Since the commercial introduction of humanized mice, antitumor efficacy studies can now be performed with human cancer cells within mice bearing the components of a human immune system. However, development and characterization of these models is necessary to understand which model may be best for different agents. To this end, we characterized A375, A549, Caki-1, H1299, H1975, HCC827, HCT116, KU19-19, MDA-MB-231, and RKO human cancer cell lines in CD34+ humanized NSG mice for tumor growth rate and immune cell profiling in tumor and spleen compartments. We found that CD4+ T cell composition in both the spleen and tumor varied among the models, with A375, Caki-1, and RKO expressing higher levels of CD4+ T cells compared to the other models. Many of the models had moderate levels of CD8+ T cells in the tumor. Spleen analysis revealed higher NK cell populations in mice bearing Caki-1 tumors, while A549 tumor samples had a higher percentage of NK cells relative to the other models. Surprisingly, many of the tumor models showed an abundance of myeloid cells in the spleen and tumor compartments, although these were mostly comprised of B cells and dendritic cells and lower levels of macrophages and MDSCs. The expression level and percentage of cells expressing PD-1, and PD-L1 in the models were also determined. Furthermore, the antitumor response of select models to PD-1 and PD-L1 antibodies will be presented. In summary, these data demonstrate that there are tumor-intrinsic factors that influence the immune cell repertoire within tumors and spleen. These data may also aid in selection of tumor models to test antitumor activity of novel IO agents. Citation Format: Christina Stevens, Christopher Maddage, Kerri Lasky, Jonathan Rios-Doria, Holly Koblish. Characterization of human cancer cell line xenografts in humanized mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1050.