Scientists have created a humanized mouse model with a human immune system, which could create antibody responses from a fully developed and functional human immune system.

The aim of the multi-year project: overcome the limitations of currently available in vivo human models by creating a humanized mouse with a human-like gut microbiome  (community of microorganisms).

The breakthrough promises new insight into immunotherapy development and disease modeling. which will appear in the August 2024 issue of Nature Immunology,

The scientists were led by Paolo Casali, MD, University of Texas Ashbel Smith Professor and Distinguished Research Professor, Department of Microbiology, Immunology and Molecular Genetics in the Joe R. and Teresa Lozano Long School of Medicine. Casali has five decades of biomedical research experience in immunology and microbiology and is a leading researcher in molecular genetics and epigenetics of the antibody response.

“Humanized” mouse model

Mice are widely used in biological and biomedical research because they are small, easy to handle, and share many immune elements and biological properties with humans. But many of the more-than 1,600 immune response mouse genes are limited.

The new humanized mice, called “TruHuX” (for truly human) or THX), possess a fully developed and fully functional human immune system, including lymph nodes, germinal centers, thymus human epithelial cells, human T and B lymphocytes, memory B lymphocytes, and plasma cells making highly specific antibody and autoantibodies identical to those of humans.

Wide range of new experiments and developments

The THX mouse discovery opens the possibilities for human in vivo experimentation, development of immunotherapeutics such as cancer checkpoint inhibitors, development of human bacterial and viral vaccines, and modeling of many human diseases. (Casali also hopes the new approach could make obsolete the use of non-human primates for immunological and microbiological biomedical research.)

The Casali lab is also investigating the in vivo human immune response to SARS-CoV-2 (COVID-19).

Citation: Chupp, D. P., Rivera, C. E., Zhou, Y., Xu, Y., Ramsey, P. S., Xu, Z., Zan, H., & Casali, P. (2024). A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses. Nature Immunology, 1-18. https://www.nature.com/articles/s41590-024-01880-3 (open access)

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