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Characterization of the Orthotopic MMTV-PyMT Murine Mammary Carcinoma Model Following Radiation and Immune Checkpoint Blockade

AACR 2020 -- The continual pressure to develop molecules that target the immune system requires that there are new, reliable and well-characterized preclinical models available. The characterization of these models must go beyond simple growth kinetics, and define the baseline immune profile in order for the models to be used to their fullest potential. The use of radiotherapy (RT), in combination with checkpoint blockade, to prime and activate the immune system is an area of intensive research, especially in breast cancer, a commonly immunogenically "cold" cancer. MMTV-PyMT was originally created as a transgenic mouse model. MMTV-PyMT tumors express the Polyoma Virus Middle T (PyMT) antigen under the direction of the mouse mammary tumor virus (MMTV) promoter. The transgenic mice spontaneously develop tumors in the mammary fat pads and ultimately develop metastatic disease to the lungs. Primary tumor material from these transgenic mice can be collected and viably stored for use in naïve mice to induce disease similar to what is observed in the transgenic mice themselves. Thus, we have optimized this model as an orthotopic transplantable model. We characterized the immune profile of orthotopically transplanted MMTV-PyMT tumors and the anti-tumor response to checkpoint inhibitors and focal RT. Immune cell infiltration into the tumors in response to checkpoint inhibitor treatments, RT, and combination therapies was examined using flow cytometry and cytokine analysis.