Dual Benefit of TGFB Inhibition on Tumor Control in the Context of Radiotherapy for Breast Cancer Brain Metastases
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2018
- Accession Number
- AD1053842
Entities
People
- Benjamin Franc
Organizations
- University of California, San Francisco