Abstract
Mice engrafted with human immune cells offer powerful in vivo model systems to investigate molecular and cellular processes of tumorigenesis, as well as to test therapeutic approaches to treat the resulting cancer. The use of umbilical cord blood mononuclear cells as a source of human immune cells for engraftment is technically straightforward, and provides T lymphocytes and autologous antigen-presenting cells (including B cells, monocytes, and DCs) that bear cognate antigen presenting molecules. By using a human-specific oncogenic virus, such as Epstein-Barr virus, de novo neoplastic transformation of the human B cells can be induced in vivo in a manner that models progressive stages of tumorigenesis from nascent neoplasia to the establishment of vascularized tumor masses with an immunosuppressive environment. Moreover, since tumorigenesis occurs in the presence of autologous T cells, this type of system can be used to investigate how T cells become suppressed during tumorigenesis, and how immunotherapies counteract immunosuppression. This minireview will provide a brief overview of the use of human umbilical cord blood transplanted into immunodeficient murine hosts to model antitumor responses.
Highlights
While animal model systems, and laboratory mouse strains, are absolutely indispensible for understanding the basic biology of both cancers and the immune system, preclinical analyses of tumor immunotherapy are likely to benefit from experimental systems that utilize primary human cells obtained from genetically diverse individuals
Key is to be able to assess in vivo responses of human T cells that are autologous to the tumor, as well as to test the impact of exogenously administered effectors (e.g., chimeric antigen receptor (CAR)-T cells) on established tumors
These elements are provided by new experimental models in which immunodeficient mice are engrafted with human immune cells, and human tumor formation is induced in vivo via infection with an oncogenic virus
Summary
Laboratory mouse strains, are absolutely indispensible for understanding the basic biology of both cancers and the immune system, preclinical analyses of tumor immunotherapy are likely to benefit from experimental systems that utilize primary human cells obtained from genetically diverse individuals. The second approach, cellular immunotherapy, involves administering cytolytic lymphocytes that have been expanded in vitro, and act as direct antitumor effectors within the patient Most prominent in this category is the use of chimeric antigen receptor (CAR) T cells that have been genetically modified to target the patient’s tumor [3]. Key is to be able to assess in vivo responses of human T cells that are autologous to the tumor (e.g., those targeted by checkpoint blockade), as well as to test the impact of exogenously administered effectors (e.g., CAR-T cells) on established tumors These elements are provided by new experimental models in which immunodeficient mice are engrafted with human immune cells, and human tumor formation is induced in vivo via infection with an oncogenic virus
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