Deaminases and Why Mice Sometimes Lie in Immuno-Oncology Pre-Clinical Trials?

Abstract

A B S T R A C TThere is now much evidence for the involvement of deaminase-mediated somatic mutagenesis during cancer progression. These developments lead us to reappraise the likely impact of AID/APOBEC and ADAR deaminases in human cancer progression with their expected lesser impact on somatic mutagenesis in mouse cancer model systems. The findings are important for pre-clinical trials of immune oncology (IO) drugs activating adaptive immune responses against tumor cells. Our conclusions are consistent with, and underline, recent recommendations by Decker and colleagues that IO pre-clinical trials should at least include therapies against spontaneous tumors in dogs. While the AID/APOBEC deaminase specificity repertoire in dogs is likely to be less than in humans, it will be far greater than in the mouse and thus more likely to better mimic dysregulated Ig like somatic hypermutation responses during cancer progression in humans.