A TRAIL-R1-specific ligand in combination with doxorubicin selectively targets primary breast tumour cells for apoptosis

Although the majority of tumour cell lines, including breast cancer cell lines, are sensitive to the death-inducing ligand and potential cancer biotherapeutic TNF-related apoptosis-inducing ligand (TRAIL), most primary tumours are TRAIL-resistant. Importantly, doxorubicin, a chemotherapeutic agent commonly used in breast cancer, has previously been shown to sensitize TRAIL-resistant breast cancer cell lines to TRAIL. Furthermore, using receptor-selective ligands (patent filed by MRC Technology) specific for the TRAIL death receptors, TRAIL-R1/TRAIL-R2, we have previously shown that primary leukaemic cells isolated from patients with chronic lymphocytic leukaemia can be selectively sensitized to apoptosis by combining an a histone deacetylase inhibitor (HDACi) with a TRAIL-R1-specific form of TRAIL/TRAIL-R1 mAb.