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Wege, A.K.* ; Ernst, W.* ; Eckl, J. ; Frankenberger, B. ; Vollmann-Zwerenz, A.* ; Männel, D.N.* ; Ortmann, O.* ; Kroemer, A.* ; Brockhoff, G.*

Humanized tumor mice - a new model to study and manipulate the immune response in advanced cancer therapy.

Int. J. Cancer 129, 2194-2206 (2011)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The immunological impact on antibody-based anticancer therapies remains incompletely understood due to the lack of appropriate animal models for in vivo analysis. Here, we present a novel humanized tumor mouse (HTM) model, generated by concurrent transplantation of human hematopoietic stem cells (HSCs) and human breast cancer cells in neonatal NOD-scid IL2Rγ(null) mice. Five weeks after intrahepatic transplantation, a functional human immune system was developed in all organs, and, in addition, tumor cells were detectable in lung and bone marrow (early dissemination). After 3 months posttransplant, tumor-cell effusions and macroscopic tumors associated with liver or spleen were found. Furthermore, disseminated cells in different lymphoid and nonlymphoid organs were measurable. Tumor growth was accompanied by specific T-cell maturation and tumor cell-specific T-cell activation. In addition, Natural-Killer cell accumulation and activation were observed in HTM, which was further enhanced upon IL-15 treatment facilitating the possibility of immune cell modulation in, e.g., antibody-dependent cellular cytotoxicity-based immunotherapeutic approaches. This novel mouse model makes it possible to combine transfer of MHC mismatched tumor cells together with human HSCs resulting in a solid coexistence and interaction without evidence for rejection. Overall, humanized tumor mice represent a powerful in vivo model that for the first time permits the investigation of human immune system-related target cancer therapy and resistance.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords humanized tumor mice; immune-based therapies; breast cancer; NK cells; ADCC
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Journal International Journal of Cancer
Quellenangaben Volume: 129, Issue: 9, Pages: 2194-2206 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
CCG Immune Monitoring (Platform) (IMI-KIM)