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

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

Author Info

Corresponding Author
Edward J. Steele
CYO'Connor ERADE Village Foundation, 24 Genomics Rise, Piara Waters, 6112, Perth, Australia

A B S T R A C T

There 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.

Article Info

Article Type
Comment/Analysis
Publication history
Received: Sat 02, Mar 2019
Accepted: Sun 17, Mar 2019
Published: Tue 30, Apr 2019
Copyright
© 2021 Edward J. Steele . This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.ACO.2019.01.001