Yvonne Paterson
University of Pennsylvania, USA
Title: HER-2/neu as a target for Listeria-based cancer immunotherapy for breast cancer
Biography
Biography: Yvonne Paterson
Abstract
We have been developing novel, live, highly attenuated bacterial vectors based on Listeria monocytogenes (Lm),rnbioengineered to secrete tumor-associated antigens and to present them to the immune system in a particularlyrnimmunogenic manner. The Lm vector itself, in addition to its major virulence factor listeriolysin O,(LLO), serves as its ownrnadjuvant and is phagocytized byAPC where it presents antigens through both MHC class I and II pathways,resulting in specificrnT-cell immunity to tumors. We have conducted extensive pre-clinical studies to determine the mechanism of action of Lm asrnan immunotherapeutic and its efficacy in numerous mouse models of cancer.Here we will describe the advancement of Lm-rnLLO immunotherapyinto the clinic for HER-2/neu over expressing tumors, such as breast cancer.Lm-LLO-cHER-2/neu,is anrnLm-LLO immunotherapy bioengineered to secrete a chimeric polypeptide consisting of three regions of HER-2/neu knownrnto contain most human HLA epitopes. This polypeptide, comprising 419 residues, about one third of the intact HER-2/neurnmolecule was fused to a truncated form of LLO for expression by Lm. Lm-LLO-cHER-2/neu has proven to be effective atrnlimiting tumor growth in pre-clinical mouse models of cancer.