Abstract
Animal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of diseases. However, mouse models do not reproduce the genetic and molecular complexity inherent in human disease conditions. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis and tumor immunobiology provide one means to bridge the interspecies gap. Natural killer cells are the founding member of the innate lymphoid cell family. They exert a rapid and strong immune response against tumor and pathogen-infected cells. Their antitumor features have long been exploited for therapeutic purposes in the context of cancer. In this review, we detail the development of highly immunodeficient mouse strains and the models currently used in cancer research. We summarize the latest improvements in adoptive natural killer (NK) cell therapies and the development of novel NK cell sources. Finally, we discuss the advantages of HIS mice to study the interactions between human NK cells and human cancers and to develop new therapeutic strategies.
Highlights
Since the generation of the first inbred mouse strains in the early 20th century, mice have served as model organisms to study mammalian biology
In vitro experiments have pointed to an increased natural killer (NK) cell-mediated lysis of lymphoma and myeloma cells with allogeneic NK cell infusion in combination with monoclonal antibodies blocking inhibitory killer cell immunoglobulin-like receptors (KIRs) but this effect need to be confirmed in vivo [86, 87]. Another strategy to increase NK cell activity without aggravating the side-effects is the expression of chimeric antigen receptors (CARs) directed against tumor antigens
NSG mice demonstrated the capacity of these cells to migrate to BM, spleen, and liver and the inhibition of leukemia growth and prolongation of mice survival when combined with low-dose IL-15 [96]
Summary
Reviewed by: Lutz Walter, Leibniz-Institute for Primate Research, Germany Philippe Saas, Etablissement Français du Sang BFC, France. Animal models have extensively contributed to our understanding of human immunobiology and to uncover the underlying pathological mechanisms occurring in the development of diseases. Human immune system (HIS) mouse models that are susceptible to human pathogens and can recapitulate human hematopoiesis and tumor immunobiology provide one means to bridge the interspecies gap. Natural killer cells are the founding member of the innate lymphoid cell family. They exert a rapid and strong immune response against tumor and pathogen-infected cells. Their antitumor features have long been exploited for therapeutic purposes in the context of cancer. We detail the development of highly immunodeficient mouse strains and the models currently used in cancer research.
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