Combining anti-CTLA4 with RG7787, an immunotoxin targeting mesothelin, promotes tumor eradication

Introduction Antibodies to cytotoxic T-lymphocyte-associated protein 4 (CTLA4) potentiate an immune response against cancer. Response rates in melanoma patients are range from 10 to 19%[1]. To increase the efficacy and variety of cancer types treated by anti CTLA4, a combination therapy should be pursued. RG7787 is a recombinant immunotoxin composed of an anti-mesothelin Fab fused to a fragment of Pseudomonas exotoxin A (PE). RG7787 is currently tested in phase 1 trials for mesothelin expressing malignancies. We previously observed that an anti-mesothelin immunotoxin produced major tumor regressions in humans with advanced mesothelioma when combined with Cytoxan and Pentostatin apparently due to T cell activation[2] and we are exploring other ways to activate the immune system when cells are killed by immunotoxin. We hypothesize that combining RG7787 with anti CTLA4 will promote activation of the immune system and cancer elimination.