A novel single domain antibody (sdAb) SBT-100 to target intracellular STAT3 to affect growth and regression of human triple negative breast cancer (TNBC) cells.

Abstract

1083Background: TNBC has limited response to chemotherapy, and poor prognosis when it metastasizes. Activated STAT3 has been shown to play an important role in the pathogenesis of TNBC. We evaluated the hypothesis that inhibition of STAT3 by a sdAb would inhibit growth of TNBC cells in vitro and in mouse xenograft studies. Methods: Human TNBC cell lines MDA-MB-231, MDA-MB-468, and MDA-MB-453 were grown in culture and treated with varying doses of SBT-100, which specifically binds human STAT3. On day 3 MTT assay were performed to assess growth inhibition. In mouse xenograft studies, human MDA-MB-231 cells were grown as tumors (size range: 77±7.17 - 104.71±14.64 mm3) in athymic mice and treated with varying doses of SBT-100 or with vehicle intraperitoneally for 14 days and observed for 7 days post treatment. Immunoprecipitation (IP) and western blot studies were performed to assess binding of STAT3 by SBT-100. Results: After 3 days of SBT-100 treatment in vitro growth suppression was as observed follows: MD...