A New Humanized Mouse Model Leads to New Opportunities in Treating Colorectal Cancer
While immunotherapy is effective in the case of many different types of cancer, colorectal cancers have always presented scientists with far greater challenges, due to being “microsatellite stable.” According to Julie Lang, PhD, the CU Cancer Center’s senior research associate, a recently developed humanized mouse model of colorectal cancer has allowed researchers to make significant progress in the application of immunotherapy for this type of cancer. The study was presented at the American Association for Cancer Research (AACR) 2017 Meeting, and it is the first to present a humanized mouse with a human-like immune system that has been genetically modified for the purpose of studying colorectal cancer.
Humanized Mice and Immunotherapy
The problem has always been to counter the natural response that a mouse’s immune system to artificially embedded tumor tissue. A mouse with a working immune system will simply attack and destroy the tumor before it gets a chance to grow. As a result, it made sense for researchers to create a traditional mouse model of cancer with an immune system that would respond the same way a human immune system would.
The procedure entails the human immune system to be transplanted into the mouse model along with the colorectal tumor. Once ready, the humanized mouse allows researchers to test various treatments, and get accurate feedback before ascertaining its efficiency in the case of human patients.
The study – led by Anna Capasso, MD, and her research team at the Colorado University School of Medicine – featured a mouse model that has been humanized through the introduction of stem cells marked by the CD34 protein. Colorectal cancer cells were then added when the mice were 16 weeks old, and the process was timed so that the tumor was engrafted before the T cells of the mice were mature, but after CD34 cells were already integrated into the mouse’s immune system.
Nivolumab immunotherapy was used in a group of mice, with a control group left untreated. The results were exactly what doctors would find when treating human patients with colorectal cancer: the tumors of the control group were visibly larger than the treated ones, due to nivolumab’s ability to prevent the deactivation of the protein PD1, which signals the body to render the immune system powerless.
The experiment was a complete success, and Capasso considers that the validated mouse model could also help with the future research and discovery of other treatments.
Future Research Approaches
Different types of approaches and drugs were already suggested with regards to the immune therapies that could be tested with the help of this mouse model.
Right now, one of the most promising approaches is that of targeting PD1 and PD-L1, as well as the gene MEK, with the help of immunotherapy. Although MEK inhibitors have not presented the desired clinical benefits, the process of MEK inhibition could be far more beneficial than any single drug when it comes to treating colorectal cancer.
Because of its unique qualities, the research team also hopes that the mouse model can be used for the design of new immunotherapies just as well as it will help with translational research. The opportunity is at hand to approach immunotherapy in entirely new ways for the purpose of treating cancer, and the mouse model is also available commercially, allowing researchers worldwide to use it successfully.