Glypican-3–Targeted <sup>227</sup>Th <b>α</b>-Therapy Reduces Tumor Burden in an Orthotopic Xenograft Murine Model of Hepatocellular Carcinoma
Kevin P. Labadie, Donald K. Hamlin, Aimee L. Kenoyer, Sara K. Daniel, Alan F. Utria, Andrew D. Ludwig, Heidi L. Kenerson, Lily Li, Jonathan G. Sham, Delphine L. Chen, Johnnie J. Orozco, Raymond S. Yeung, Chris Orvig, Yawen Li, D. Scott Wilbur, James O. Park
Abstract
Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality worldwide with limited therapeutic options for advanced disease. Targeted alpha therapy (TAT) is an emerging class of targeted cancer therapy in which alpha-particle-emitting radionuclides, such as thorium-227, are specifically delivered to cancer tissue. Glypican-3 (GPC3) is a cell surface glycoprotein highly expressed on HCC. In this study, we describe the development and in vivo efficacy of a 227 Th-labeled GPC3 targeting antibody conjugate ( 227 Th-octapa-GPC3) for treatment of HCC in an orthotopic murine model.