The Development of Next-generation PBMC Humanized Mice for Preclinical Investigation of Cancer Immunotherapeutic Agents

Investigation of the efficacy and mechanisms of human immuno-oncology agents has been hampered due to species-specific differences when utilizing preclinical mouse models. Peripheral blood mononuclear cell (PBMC) humanized mice provide a platform for investigating the modulation of the human immune-...

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Bibliographic Details
Published inAnticancer research Vol. 40; no. 10; pp. 5329 - 5341
Main Authors MORILLON, Y. MAURICE, SABZEVARI, ARIANA, SCHLOM, JEFFREY, GREINER, JOHN W.
Format Journal Article
LanguageEnglish
Published Athens International Institute of Anticancer Research 01.10.2020
Subjects
Animal models
Antitumor activity
Cancer
Cancer immunotherapy
Cell culture
Graft-versus-host reaction
Oncology
Peripheral blood mononuclear cells
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Summary:Investigation of the efficacy and mechanisms of human immuno-oncology agents has been hampered due to species-specific differences when utilizing preclinical mouse models. Peripheral blood mononuclear cell (PBMC) humanized mice provide a platform for investigating the modulation of the human immune-mediated antitumor response while circumventing the limitations of syngeneic model systems. Use of humanized mice has been stymied by model-specific limitations, some of which include the development of graft versus host disease, technical difficulty and cost associated with each humanized animal, and insufficient engraftment of some human immune subsets. Recent advances have addressed many of these limitations from which have emerged humanized models that are more clinically relevant. This review characterizes the expanded usage, advantages and limitations of humanized mice and provides insights into the development of the next generation of murine humanized models to further inform clinical applications of cancer immunotherapeutic agents.
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Authors’ Contributions
Writing of the article was performed by YMM, AS, and JWG. Review of the literature was performed by YMM, AS, and JWG. Review and approval of the article was performed by JWG and JS.
These Authors contributed equally to this article.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.14540