Techniques for the generation of humanized mouse models for immuno-oncology

Mouse models of human cancer have been used extensively to circumvent the complexity in human patients. However, murine models often inadequately recapitulate the human cancer-immune interface partly due to important differences between mouse and human immune systems. Immunodeficient mice when transplanted with CD34⁺ hematopoietic progenitor cells (HPCs) develop multilineage human immune cells. While there remain limitations, efforts have been made to improve the function of human immune system. Thus, humanized mice, defined as mice with human immune system, have become an emerging model to study human cancers. Humanized mouse models have been used for various areas of cancer research including adoptive transfer of chimeric antigen receptor (CAR)-modified T cells, neoantigen vaccination to increase T cell repertoire and reprograming tumor microenvironment. Here, we describe the essential techniques to generate humanized mouse models for immuno-oncology studies.