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

Document Type

Article

Publication Date

2020

Keywords

JGM

JAX Source

Meth Enzymol 2020; 636:351-368

Volume

636

First Page

351

Last Page

368

ISSN

1557-7988

PMID

32178826

DOI

https://doi.org/10.1016/bs.mie.2019.06.003

Grant

CA195712,CA219880,Department of Defense (W81XWH-17-1-0010) and The Jackson Laboratory

Abstract

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.

Comments

We thank patients and healthy donors for participation in our studies over the years. We thank Dr. Jim Keck and Dr. Lenny Shultz for collaboration and Vanessa K. P. Oliveira for help with experiments. Support over the years came from Baylor Institute for Immunology Research and Baylor University Medical Center Foundation.

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