Combination of cancer immunotherapy with inhibitors of glutamine metabolism

Abstract

The focus of this thesis was the combination of immunotherapy with glutamine metabolism inhibitors. Glutamine analogs such as 6-diazo-5-oxo-L-norleucine (DON) have been known for many decades; however, their use has been limited due to severe side effects. In this study, we focused on DON and its prodrug LTP607 and tested its combination with immunotherapy that includes mannan-BAM, Toll-like receptor ligands, anti-CD40 antibodies in the rather aggressive pancreatic adenocarcinoma model. The main objective of the study was to compare the side effects of DON and its prodrug, to study the efficiency of this combination against secondary tumors, and to evaluate the influence of such a combination on the survival of mice.