Researchers have used human blood stem cells to grow a human-like immune system in mice, an advance that enables testing of anti-cancer therapies in an environment much more akin to that found in actual patients.
Human tumours grown in mouse models have long been used to test promising anti-cancer therapies. However, when a human tumour is transplanted into a mouse, the mouse immune system must be knocked down so that it doesn't attack the foreign tumour tissue, thus allowing the tumour to grow.
Researchers from the University of Colorado Cancer Center have developed a new model, XactMice, in which human blood stem cells are used to grow a "humanised" mouse immune system prior to tumour transplantation.
Now, with a human-like immune system interacting with a human-like tumour in this model, researchers can test anti-cancer therapies in an environment much more akin to that found in real patients.
The new model may be especially important in testing immunology-based therapies, which attempt to recruit the immune system to target tumour tissues.
"One of the reasons that anti-cancer immune therapies have been difficult to develop is that perhaps we haven't had adequate models. Now we have a model that will enable some of those studies," said Antonio Jimeno, the paper's senior author and director of the University of Colorado School of Medicine's Head and Neck Cancer Clinical Research Programme.
"We essentially did a bone marrow transplant on those mice," said Dr Yosef Refaeli, co-corresponding author and faculty member in the Dermatology Department and Gates Center.
Mice were treated with radiation to knock down the existing blood system and then human stem cells from human cord blood were introduced to regrow the blood system with elements of the human immune system.
"After a few months, the mice became chimeras - with human blood cells and hence a human immune system," Refaeli said.
A protocol aiming at improving humanised models from human patients is currently recruiting patients at the University of Colorado Cancer Center, researchers said.
First, small tumour samples will be taken from melanoma and also head and neck cancer patients. Blood stem cells from these patients will be used to "humanise" mice, and then patients' tumours will be grown on mice matched with their immune systems.
The mice will then be treated with anti-cancer therapies, and the results will be compared with results in the human patients.
The research is published in the journal Oncogene.
