As Harry Potter characters use an invisibility cloak to avoid detection in Hogwarts’ forbidden areas, cancer cells make themselves invisible to the immune system to avoid destruction. The recent advent of immune-directed therapies that remove this “invisibility cloak” from the surface of cancer cells has opened up a new horizon of opportunity, but also a new set of challenges.
A key difficulty has been that previous animal models of cancer depend on wiping out a rodent’s immune system so that it won’t attack tumor cells it sees as foreign. But without an immune system, the models can’t teach us how cancer evades immune surveillance, nor can they test immunotherapies, whose actions depend on the presence of an immune system.
Antonio Jimeno, MD, PhD, has developed potential solutions to this problem. He recently renewed a 5-year NIH R01 grant with a new focus on studying how head and neck cancer stem cells trick the immune system. Nearly simultaneously, Jimeno obtained another R01 grant to develop new animal models of melanoma that allow the study and testing of immunotherapies against cancer. Jimeno is director of the Head and Neck Cancer Clinical Research Program at the University of Colorado Cancer Center, a member of the Gates Center for Regenerative Medicine, and the Daniel and Janet Mordecai Endowed Chair for Cancer Stem Cell Research at the CU School of Medicine.
Jimeno’s solution has been to transplant a human immune system along with human tumor samples to create “humanized” animal models. These models with both cancer and an intact immune system allow researchers to test the ability of new drugs and treatments to turn the immune system against cancer.
Jimeno’s previous R01 grant focused on characterizing head and neck cancer stem cells, resulting in a major paper in the Journal of the National Cancer Institute describing the mechanisms by which cancer stem cells regulate the disease. The renewal and refocusing of this grant extends the work by using Jimeno’s understanding of cancer stem cells to create fully individualized models of cancer, using a patient’s immune and tumor cells to make personalized models of the disease. By comparing the effects of immunotherapies in patients with the effects of immunotherapies in these individualized tumor/immune models, Jimeno hopes to show that drugs have the same effect in mice as they do in humans, suggesting that his models could be used to explore the effectiveness of new therapies as well.
His second R01 grant hopes to develop a similar model for melanoma, a condition that has been at the forefront of developing immunotherapies. Specifically, the grant will allow Jimeno to generate individualized (with a patient’s tumor), humanized (with a patient’s immune system) models from 20 melanoma patients to study how treatment with immunotherapy correlates in the patient and in the model. This effort will be shared as part of a national network of mammalian models to study cancer, firmly establishing Jimeno’s group and CU Cancer Center as leaders in immunocompetent models of human cancer.