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Humanized Mouse Models for the Preclinical Assessment of Cancer Immunotherapy

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Abstract

Immunotherapy is one of the most exciting recent breakthroughs in the field of cancer treatment. Many different approaches are being developed and a number have already gained regulatory approval or are under investigation in clinical trials. However, learning from the past, preclinical animal models often insufficiently reflect the physiological situation in humans, which subsequently causes treatment failures in clinical trials. Due to species-specific differences in most parts of the immune system, the transfer of knowledge from preclinical studies to clinical trials is eminently challenging. Human tumor cell line-based or patient-derived xenografts in immunocompromised mice have been successfully applied in the preclinical testing of cytotoxic or molecularly targeted agents, but naturally these systems lack the human immune system counterpart. The co-transplantation of human peripheral blood mononuclear cells or hematopoietic stem cells is employed to overcome this limitation. This review summarizes some important aspects of the different available tumor xenograft mouse models, their history, and their implementation in drug development and personalized therapy. Moreover, recent progress, opportunities and limitations of different humanized mouse models will be discussed.

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Acknowledgements

The author thanks Prof. Gero Brockhoff (Department of Gynecology and Obstetrics, University Medical Center Regensburg) for carefully proofreading the manuscript and for all his helpful suggestions.

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  1. Department of Gynecology and Obstetrics, University Medical Center Regensburg, Landshuter Straße 65, 93053, Regensburg, Germany

    Anja Kathrin Wege

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Wege, A.K. Humanized Mouse Models for the Preclinical Assessment of Cancer Immunotherapy. BioDrugs 32, 245–266 (2018). https://doi.org/10.1007/s40259-018-0275-4

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