Targeting Tissue Factor for Immunotherapy of Triple-Negative Breast Cancer Using a Second-Generation ICON

摘要: Triple-negative breast cancer (TNBC) is a leading cause of death and often associated with BRCA1 BRCA2 mutation. Due to the lack validated target molecules, no targeted therapy for TNBC approved. Tissue factor (TF) common yet specific surface receptor cells, tumor vascular endothelial stem cells in several types solid cancers, including cancer. Here, we report evidence supporting idea that TF TNBC. We used vitro lines vivo xenografts mice, all or mutations, derived from patients' tumors. showed overexpressed on neovasculature 50% 85% patients (n = 161) cell line-derived (CDX) patient-derived (PDX) but was not detected adjacent normal tissue. then describe development second-generation TF-targeting immunoconjugate (called L-ICON1, lighter light chain ICON) improved efficacy safety profiles compared original ICON. L-ICON1 kills via antibody-dependent cell-mediated cytotoxicity can be treat human murine CDX as well PDX orthotopic mouse models. Thus, could useful immunotherapeutics patients, without mutations. Cancer Immunol Res; 6(6); 671-84. ©2018 AACR.