Studying the responses of the human immune system to specific antigens in vivo for vaccine development has been limited by ethical and practical concerns. Up to now all of the in vivo preclinical testing for cancer vaccine development have been performed in various animal models. Although successful stimulation of antitumor immunity has been demonstrated by many therapeutic maneuvers in animal models, the outcome of subsequent clinical applications is less encouraging due to, at least in part, the limitations of currently used animal models, the most important of which is the inability to accurately mimic the human immune system in initiating and maintaining the immune responses. Therefore, an animal model that mimics or consists of crucial components of the functional human immune system will be valuable for vaccine development and testing. The first breakthrough came with the discovery of the severe combined immunodeficiency (SCID) mouse and its ability to sustain engrafted human cells, albeit at a low level. Since that discovery, several new strains of mice have been developed to improve human leukocyte, including stem cell, engraftment and their differentiation to functional human immune cells. The most recent models consist of mice with a mutation of the interleukin-2 receptor γ chain (IL2Rγc null) in the NOD/SCID background. This IL2Rγc null genotype led to mice with significantly decreased innate immunity that allows increased levels of human cell engraftment and multilineage development of human immune cells. With further improvements, these mouse models may help in the understanding of the complex human immune responses to cancers and infectious diseases and assist in preclinical evaluation of vaccine regimens.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)