Dual Benefit of TGFB Inhibition on Tumor Control in the Context of Radiotherapy for Breast Cancer Brain Metastases
Technical Report,01 Feb 2017,31 Jan 2018
University of California San Francisco San Francisco United States
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This project evaluates whether TGF beta inhibition during radiation therapy RT to breast cancer brain metastases BCBM provides greater therapeutic benefit than RT alone using a proof-of-concept therapeutic protocol in combination with innovative functional imaging that can demonstrate efficacy in an in vivo system. In year 1 of this two-year project, we generated and characterized two syngeneic mouse models of triple negative breast cancer TNBC brain metastasis. We provided image guided radiotherapy IGRT to murine BCBM using the small animal radiation research platform SARRP and assessed the benefit of TGF beta inhibition in the context of IGRT. We assessed tumor microenvironment TME and immune system characterization as a function of radiotherapy and in combination with TGF beta blockade 1D11. In order to monitor active TGF beta in vivo, we synthesized and characterized 89Zr-DFO-fresolimumab in vivo. We imaged tumor metabolism, tumor growth, and activated T cells associated with immunological response to tumor over the natural progression of the untreated control arm of the study. In year 2 of this project, we will ascertain the benefit of including TGF inhibition in addition to targeted radiation in these BCBM models and determine whether this endorses response to immunotherapy. We will complete our functional imaging methods to assess drug distribution, tumor burden and immunological response to therapy in the treatment arm.
- Medicine and Medical Research