Abstract
Abstract Syngeneic mouse models are the most extensively explored mouse models for evaluation of immune-oncology therapeutic modalities in preclinical settings. One of the major limitations with syngeneic models is that both the tumor and the immune system is murine and thus do not express any human targets. Also, this precludes the evaluation of human clinical product (antibody or protein) mandating the synthesis and use of murine surrogates. Therefore, development of models of human tumors in mice with competent human immunity became an urgent need. Tumor-bearing, humanized NOG-EXL mice are a new and valuable preclinical testing platform for immuno-oncology, to simulate trials, evaluate multiple drugs alone or in combination, and produce predictive data both in cell line derived (CDX) and patient derived (PDX) models. With the objective of understanding the tumor growth and basal immune microenvironment in Hu-NOG-EXL mice (NOG mice humanized using CD34+ cells isolated from cord blood), we implanted three different human tumor cell lines (A549: Human Lung Carcinoma; MDA-MB-436: Triple Negative Breast Cancer; A375: Human Melanoma) in Hu-NOG EXL mice procured from Taconic, NY. The tumors were collected at a tumor volume of 1000-1500mm3, and profiled for the lymphoid and myeloid compartments using flow cytometry. The corresponding splenic compartment was also profiled to monitor the correlation or lack thereof between the tumor and splenic compartments. Finally the tumors were compared and categorized based on their basal infiltrates. The results demonstrated that Hu-NOG-EXL mice could be an useful tool to dissect the immune response in human tumors. It was possible to identify and quantitate the myeloid cells which are absent in a model that has been implanted with human PBMNC's (Peripheral Blood Mono Nuclear Cells) instead of human CD34 stem cells. Citation Format: Srimoyee Ghosh, Anne Fiore, Christoph Eberle, Sarah Wang, Keith Mikule, Kristen McEachern, Sujatha Kumar, David Jenkins, Geeta Sharma. Characterization of tumor growth and immune microenvironment in humanized NOG-EXL mice implanted with A549, MDA-MB-436 and A375 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 5690.
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