Xenograft Models of Immunodeficient Mice in Cancer Research 

Numerous mouse and rat Xenograft models have been developed to accept patient-derived xenografts. These models are typically severely immunodeficient or contain a human immune system to prevent the rejection of foreign tissue.  

For PDX studies, nude mice (without T cells) and SCID mice (without T and B cells) were used4. Xenografts are accepted because immunodeficiency prevents host immune responses from attacking them5. GEM (genetically engineered mice) have modified genomes that result in a lack of B and T cells, which are also viable options for xenograft studies. A mouse model with a Rag2 gene disruption is one example. Homozygous mice with this modification fail to produce mature B and T lymphocytes because they cannot initiate V(D)J recombination. 

Xenograft studies have recently moved towards using even more immunodeficient models, such as the CIEA NOG mouse®, even though all of these models are considered immunodeficient. Patients-derived tumors can be engrafted and grow more effectively in this model. 

The original development of this GEM was done by Mamoru Ito (CIEA) in Japan. T, B, and NK cells are not mature in this model, complement activity is reduced, macrophages and dendritic cells are dysfunctional, and T and B cells do not leak over time. It has been demonstrated that this model is an excellent platform for xenograft studies because of all of these characteristics. 

Humanized Mice

Using humanized mice, researchers can now engraft tumors into mice that contain a human immune system. Human hematopoietic stem cells have been engrafted in multiple models into NOG backgrounds. The peripheral blood, bone marrow, thymus, and spleen will contain human lymphocytes after stable engraftment of human stem cells. Patient-derived tumor models provide an invaluable platform for studying new immunotherapies.