Johns Hopkins University, USA
Title: Mark cancer cells for CTL attack through coating with viral antigenic peptides CTLs kill tumor with viral peptides
Dr. Chien-Fu Hung is an associate professor of pathology and oncology and a professor of gynecology and obstetrics at the Johns Hopkins University School of Medicine. His research focuses on the prevention and treatment of cervical and ovarian cancers. His team is currently using an ascitogenic ovarian/peritoneal tumor model to investigate DNA vaccine strategies encoding ovarian tumor antigens identified by microarray and SAGE. Dr. Hung earned his Ph.D. in molecular biology from the University of Illinois. He completed a fellowship in pharmacology at the University of Pennsylvania and a fellowship in pathology at the Johns Hopkins University. He received a Young Investigator Award from the Alliance for Cancer Gene Therapy in 2004.
Selectively coating tumor cells with foreign antigenic peptide may render coated tumor susceptible to immune recognition and elimination, thereby bypassing immune tolerance. Here we create a therapeutic chimeric protein comprised of a tumor-homing module fused to a functional cargo domain containing foreign antigenic peptide. The tumor-homing module is comprised of mesothelin-specific single chain variable fragment that specifically binds to mesothelin, commonly overexpressed in ovarian tumors. The functional cargo domain is comprised of Fc (IgG2a) protein and MHC class I-restricted foreign CD8+ T cell epitope flanked by furin cleavage sites, which can be recognized by furin highly expressed in the tumor microenvironment. We show that our therapeutic protein specifically loaded antigenic epitope onto MHC class I of bound tumor cells, rendering them susceptible to antigen-specific CD8+ T cell-mediated killing for potent antitumor effects in vitro and in vivo. Our findings have important implications for bypassing immune tolerance to enhance cancer immunotherapy.
Speaker PPTsDownload PPT