Breast Cancer

Biography

Biography: Yvonne Paterson

Abstract

We have been developing novel, live, highly attenuated bacterial vectors based on Listeria monocytogenes (Lm), bioengineered to secrete tumor-associated antigens and to present them to the immune system in a particularly immunogenic manner. The Lm vector itself, in addition to its major virulence factor listeriolysin O, (LLO), serves as its own adjuvant and is phagocytized by APC where it presents antigens through both MHC class I and II pathways, resulting in specific T-cell immunity to tumors. We have conducted extensive pre-clinical studies to determine the mechanism of action of Lm as an immunotherapeutic and its efficacy in numerous mouse models of cancer. Here we will describe the advancement of Lm-LLO immunotherapy into the clinic for HER-2/neu over expressing tumors, such as breast cancer. Lm-LLO-cHER-2/neu, is an Lm-LLO immunotherapy bioengineered to secrete a chimeric polypeptide consisting of three regions of HER-2/neu known to contain most human HLA epitopes. This polypeptide, comprising 419 residues, about one third of the intact HER-2/neu molecule was fused to a truncated form of LLO for expression by Lm. Lm-LLO-cHER-2/neu has proven to be effective at limiting tumor growth in pre-clinical mouse models of cancer.