The classic lab mouse is black or white, eats a precisely measured diet to keep him lean, and is relatively young — probably a teenager or young adult in rodent years. His genes are nearly identical to the others around him, the result of generation upon generation of inbreeding for research purposes.
Those specs might help a scientist standardize her experiments, but they may also be holding some research back for one type of cancer drug, two St. Louis researchers argued in a recent review. Instead, they say that pre-clinical trials should include older mice, obese mice, and mice with different types of gut microbiota.
“You use very, very similar mice — but people aren’t like that. Even people who are related,” said Ryan Teague, a St. Louis University microbiologist. “That poses a major problem when you’re predicting how a new therapy is going to work in patients.”
The new therapies in question are cancer immunotherapy treatments, which boost a person’s immune system to attack a tumor. Some clinical trials have hit snags, because the drugs were too toxic for patients to continue the treatment. In the paper, Teague argues that may be because the mice used to model the treatments are generally young and lean, while most cancer patients are older than 65, and about a third of Americans are obese. The model doesn’t match.
“The very few studies that have been done indicate that obesity and increased age absolutely increases the risk of toxicity from immunotherapy,” Teague said. “But the research has been sparse so far.”
Part of that, Teague surmises, is due to the cost of taking care of mice until they reach old age or can increase their body mass to an obese state.
“We get charged every day for a mouse cage, and for mice that typically live six to eight weeks… those prices skyrocket when you’re talking about mice that have to be maintained for 12 to 18 months, and in large enough numbers to do a statistically powerful experiment,” Teague said.
The researchers recommend conducting trials that compare young, old, lean and obese mice, as well as studying variations in microbes found in their intestinal tracts.
The theory is also being applied to vaccine research at Washington University in St. Louis, where scientists infected lab mice with herpes, flu viruses and intestinal worms to model a human immune system. At the University of Minnesota, Twin Cities, researchers put lab mice in the same cages as mice purchased from a pet store, to see how their immune systems reacted while fighting off unfamiliar infections. The mice that survived, researchers argued, are more accurate models for humans.
The review by Teague and co-author Lauryn Klevorn, "Adapting Cancer Immunotherapy Models for the Real World," appears in the June issue of Trends in Immunology.
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