Sequential infection of laboratory mice for enhanced cancer and immunotherapy translation

ABSTRACT
Mouse models have been tremendously important to understand and develop treatments for
humans. Yet, from an immune perspective, mouse models resemble an immature immune
system, including lack of microbiota adaptations, infections, and vaccinations that humans
encounter early in life to shape immune maturation. Use of wild-caught mice that have a more
adult-like immune system has helped to better understand the adult immune response; however,
these mice have a series of practical and genetic issues that preclude their widespread use. We
hypothesize that the neonatal like immune system in Specific Pathogen Free (SPF) mice that are
normally used in the laboratory underlies many of the differences observed between mouse and
human anti-tumor responses and the translatability of therapeutic approaches. To overcome this,
we will adapt and develop a strategy to produce lab-generated “wild-like” mice that mimic the
immune response observed in adults. We propose that these lab-generated “wild-like” mice will
recapitulate the adult human immune system and mimic the responses to cancer and
immunotherapy observed in humans. This approach of immune education is performed on
otherwise wild-type mice, enabling wide-spread adoption to foster cancer studies.

Grant Number: 1R21CA296062-01A1
NIH Institute/Center: NIH
Principal Investigator: DAVID BROOKS