Wege, Anja K. and Ernst, Wolfgang and Eckl, Judith and Frankenberger, Bernhard and Vollmann-Zwerenz, Arabel and Maennel, Daniela N. and Ortmann, Olaf and Kroemer, Alexander and Brockhoff, Gero (2011) Humanized tumor mice-A new model to study and manipulate the immune response in advanced cancer therapy. INTERNATIONAL JOURNAL OF CANCER, 129 (9). pp. 2194-2206. ISSN 0020-7136,
Full text not available from this repository. (Request a copy)Abstract
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 IL2R gamma(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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEPENDENT CELLULAR CYTOTOXICITY; NATURAL-KILLER-CELLS; IN-VIVO; MONOCLONAL-ANTIBODIES; BREAST-CANCER; NK-CELL; GROWTH; IL-15; MOUSE; HIV-1; humanized tumor mice; immune-based therapies; breast cancer; NK cells; ADCC |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 May 2020 13:59 |
| Last Modified: | 28 May 2020 13:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19949 |
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