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.