Glowing Head Mice: A Genetic Tool Enabling Reliable Preclinical Image‐Based Evaluation of Cancers in Immunocompetent Mice

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NCI	CANCER-8

Authors

• CP Day
• J Carter
• ZW Ohler
• C Bonomi
• R El Meskini
• P Martin
• C Graff-Cherry
• L Feigenbaum
• T Tüting
• T Van Dyke
• M Hollingshead
• G Merlino

Abstract

Preclinical therapeutic assessment currently relies on the growth response of established human cell lines xenografted into immunocompromised mice, a strategy that is generally not predictive of clinical outcomes. Immunocompetent genetically engineered mouse (GEM)-derived tumor allograft models offer highly tractable preclinical alternatives and facilitate analysis of clinically promising immunomodulatory agents. Imageable reporters are essential for accurately tracking tumor growth and response, particularly for metastases. Unfortunately, reporters such as luciferase and GFP are foreign antigens in immunocompetent mice, potentially hindering tumor growth and confounding therapeutic responses. Here we assessed the value of reporter-tolerized GEMs as allograft recipients by targeting minimal expression of a luciferase-GFP fusion reporter to the anterior pituitary gland (dubbed the “Glowing Head” or GH mouse). The luciferase-GFP reporter induced adverse immune responses to tumor cells transplanted into wildtype relative to GH mice. Growth and metastatic potential of labeled tumors, as well as their responses to chemo- and targeted-therapies, were significantly altered in GH compared to wildtype mice. Thus the GH mice and experimental approaches vetted herein provide concept validation and a strategy for effective, reproducible preclinical evaluation of growth and response kinetics for traceable tumors.

back to top