AMATUXIMAB Chimeric Anti-Mesothelin Monoclonal Antibody Treatment of Mesothelioma

Mesothelin-expressing adenocarcinomas, such as ovarian, pancreatic, lung or mesothelial cancers, are tumors which usually bear a high invasive potential and for which conventional cytotoxic therapies are not always effective. Mesothelin has evolved as a biomarker, as well as a therapeutic target in oncology, based on demonstration of the correlation of its serum titers with tumor activity in mesothelin-positive cancers, and on the demonstration of tumor regression as a result of the specific mesothelin blockade with various types of compounds. Among these, monoclonal antibodies were the first to be developed and tested experimentally for their antibody-mediated cytotoxic potential in animal models of mesothelin-positive cancers. Amatuximab (MORAb-009) is a chimeric antibody developed from a mouse prototype initially used for research purposes and which was then optimized in terms of binding affinity and subsequently humanized to reach the present structure. This antibody is currently investigated in clinical studies for its ability to be used as a molecular imaging agent in evaluating tumor dynamics and activity, and it is also being tested in phase II studies in advanced mesothelin-positive cancer as a standalone therapy or as an add on to conventional cytotoxic agents.