Humanized tumor mice-A new model to study and manipulate the immune response in advanced cancer therapy
| Autor: | Daniela N. Männel, Olaf Ortmann, Arabel Vollmann-Zwerenz, Judith Eckl, Bernhard Frankenberger, Wolfgang Ernst, Anja K. Wege, Alexander Kroemer, Gero Brockhoff |
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| Rok vydání: | 2011 |
| Předmět: |
Graft Rejection
Cancer Research T-Lymphocytes medicine.medical_treatment Breast Neoplasms Mice SCID humanized tumor mice immune-based therapies breast cancer NK cells ADCC Hematopoietic stem cell transplantation Biology Mice 03 medical and health sciences 0302 clinical medicine Immune system Mice Inbred NOD Cell Line Tumor medicine Animals Humans 030304 developmental biology Interleukin-15 Mice Knockout Antibody-dependent cell-mediated cytotoxicity 0303 health sciences Hematopoietic Stem Cell Transplantation 3. Good health Killer Cells Natural Transplantation Disease Models Animal medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer cell Immunology biology.protein Female Bone marrow Stem cell Antibody |
| Zdroj: | International Journal of Cancer; Vol 129 Int. J. Cancer 129, 2194-2206 (2011) International Journal of Cancer |
| ISSN: | 0020-7136 |
| DOI: | 10.1002/ijc.26159 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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