Samir A. Farghaly
Cornell University, USA
Title: Mesothelin Expression in Ovarian Cancer and its potential as Targeted Ovarian cancer Immunotherapy
Biography
Biography: Samir A. Farghaly
Abstract
Ovarian cancer is the fourth most common cause of cancer death in women. Most patients are diagnosed at stage III and IV, with resultant low relative-survival rates. The current treatments with conventional cytotoxic chemotherapy and novel surgical techniques have improved the oncologic outcome of this disease. However,recurrence is common. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is of significant importance in preventing recurrence. Immunotherapy for ovarian cancer is to balance the activation of the immune system against this cancer while preventing the potential for toxicity elicited by immune modulation. Mesothelin, a glycosylphosphatidylinositol (GPI) anchored cell surface protein, is a potential target for antibody-based ovarian cancer immunotherapy due to its high expression in ovarian cancer. Mesothelin plays a role in cancer ovarian progression, through three possible mechanisms. First, mesothelin may aid in the peritoneal implantation and metastasis of tumors through its interaction with mucin MUC16 (CA125). Second, mesothelin may promote cancer cell survival and proliferation via the NF-κB signaling pathway. Third, mesothelin expression promotes resistance to certain chemotherapy drugs such as TNF-α, paclitaxel, and a combination of platinum and cyclophosphamide. Human monoclonal antibodies targeting mesothelin have been isolated by phage display technology and may provide opportunities for novel ovarian cancer immunotherapy. In addition, CRS-207, is live-attenuated Listeria monocytogenes (Lm), which has been genetically modified to be safe for human use while retaining its ability to stimulate an immune response against the protein mesothelin. It is considered an active form of immunotherapy. It utilizes a live attenuated facultative intracellular bacterium, Listeria monocytogenes, as a vehicle to deliver the mesothelin antigen to kupffer cells . Once the bacteria undergo phagocytosis, both innate and adaptive immune responses occur. Ultimately, this leads to mesothelin-specific T-cell response directed toward ovarian cancer cells overexpressing mesothelin.