Development Of Targeted Radiotherapy For Triple Negative Breast Cancer.

e13112Background: Breast cancer (BC) remains a leading cause of cancer-related deaths worldwide. Triple negative breast cancer (TNBC) is an aggressive phenotype that comprises only 15-20% of all new BC cases but is responsible for a majority of related deaths. Chemotherapy is the current mainstay treatment for TNBC but side effects and drug-resistance remain an issue, so development of targeted therapies for TNBC is critical. Tumor associated mucin 1 (tMUC1), an aberrantly glycosylated transmembrane glycoprotein, is overexpressed in u003e 90% of TNBCs. We’ve developed a humanized, tMUC1-specific antibody (hTAB004) and radiolabeled it to allow for targeted TNBC treatment. Methods: hTAB004 was conjugated to DOTA-NHS, purified, formulated in a metal free buffer and radiolabeled with Indium-111 or Actinium-225 to produce 111In-DOTA-hTAB004 and 225Ac-DOTA-hTAB004, respectively. In vivo and ex vivo biodistribution studies of 111In-DOTA-hTAB004 were performed in HCC70 xenograft tumor-bearing female NSG mice (n = 3) ...