Abstract 5607: Tissue factor is a novel oncotarget for immunotherapy of triple-negative breast cancer using a second generation ICON in orthotopic mouse models of human and murine TNBC cell line- and patient-derived xenografts

Abstract

Abstract Triple-negative breast cancer (TNBC) is often associated with BRCA1 and BRCA2 mutation and is a leading cause of breast cancer death. Due to the lack of validated target molecules, there is currently no approved targeted therapy for TNBC. Tissue factor (TF) is a common yet specific surface target receptor for cancer cells, tumor vascular endothelial cells and cancer stem cells in several types of solid cancers. Here we report evidence supporting the idea that TF is a novel surface target for TNBC patients and cancer lines with BRCA1 and BRCA2 mutations. We showed that TF is over-expressed on TNBC cells and tumor neovasculature in greater than 85% of TNBC patients (n=14) when using standard paraffin-embedded tumor tissues and in nearly 60% of TNBC patients (n=157) when employing tissue microarray slides, but was not detected in adjacent normal breast tissue. We also describe the development of a second-generation TF-targeting immunoconjugate with improved efficacy and higher safety threshold compared to the original immunoconjugate. We showed that L-ICON1 is effective in killing TNBC cells via antibody-dependent cell-mediated cytotoxicity in vitro and in treating human and murine TNBC cell line- and patient-derived xenografts in vivo in preclinical orthotopic mouse models. These results suggest that TF is a novel oncotarget in TNBC and targeting TF may constitute a novel targeted immunotherapy for TNBC patients. The findings in this preclinical study warrant further clinical investigation. Citation Format: Zhiwei Hu, Rulong Shen, Amanda Campbell, Elizabeth McMichael, Lianbo Yu, Bhuvaneswari Ramaswamy, Cheryl A. London, Tian Xu, William E. Carson. Tissue factor is a novel oncotarget for immunotherapy of triple-negative breast cancer using a second generation ICON in orthotopic mouse models of human and murine TNBC cell line- and patient-derived xenografts [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 5607.