A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect
| Autor: | Ellen van der Spek, Richard W.J. Groen, Vivienne Verweij, Tuna Mutis, Henk Rozemuller, Maarten E. Emmelot, Anton C.M. Martens, Henk M. Lokhorst, Lijnie Bogers-Boer, Andries C. Bloem, Robbert M. Spaapen, Mieke C. Zwart |
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| Přispěvatelé: | Hematology laboratory, CCA - Cancer biology and immunology, Hematology, CCA - Cancer Treatment and quality of life |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Pathology medicine.medical_treatment Mice Transgenic Peripheral blood mononuclear cell Cell therapy Mice Cell Line Tumor Internal medicine medicine Animals Humans Bioluminescence imaging Multiple myeloma Cell Proliferation Hematology business.industry Graft vs Tumor Effect Immunotherapy medicine.disease Disease Models Animal Luminescent Proteins Retroviridae Treatment Outcome medicine.anatomical_structure Tumor progression Disease Progression Bone marrow Multiple Myeloma business Neoplasm Transplantation |
| Zdroj: | Haematologica, 93(7), 1049-57. Ferrata Storti Foundation Rozemuller, H, van der Spek, E, Bogers-Boer, L H, Zwart, M C, Verweij, V, Emmelot, M, Groen, R W, Spaapen, R, Bloem, A C, Lokhorst, H M, Mutis, T & Martens, A C 2008, ' A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect ', Haematologica, vol. 93, no. 7, pp. 1049-57 . https://doi.org/10.3324/haematol.12349 |
| ISSN: | 0390-6078 |
| DOI: | 10.3324/haematol.12349 |
| Popis: | BACKGROUND: The development and preclinical testing of novel immunotherapy strategies for multiple myeloma can benefit substantially from a humanized animal model that enables quantitative real-time monitoring of tumor progression. Here we have explored the feasibility of establishing such a model in immunodeficient RAG2(-/-)gammac(-/-) mice, by utilizing non-invasive bioluminescent imaging for real-time monitoring of multiple myeloma cell growth.DESIGN AND METHODS: Seven multiple myeloma cell lines, marked with a green fluorescent protein firefly luciferase fusion gene, were intravenously injected into RAG2(-/-)gammac(-/-) mice. Tumor localization and outgrowth was monitored by bioluminescent imaging. The sensitivity of this imaging technique was compared to that of free immumoglobulin light chain -based myeloma monitoring. Established tumors were treated with radiotherapy or with allogeneic peripheral blood mononuclear cell infusions to evaluate the application areas of the model.RESULTS: Five out of seven tested multiple myeloma cell lines progressed as myeloma-like tumors predominantly in the bone marrow; the two other lines showed additional growth in soft tissues. In our model bioluminescent imaging appeared superior to free light chain-based monitoring and also allowed semi-quantitative monitoring of individual foci of multiple myeloma. Tumors treated with radiotherapy showed temporary regression. However, infusion of allogeneic peripheral blood mononuclear cells resulted in the development of xenogeneic graft-versus-host-disease and a powerful cell dose-dependent graft-versus-myeloma effect, resulting in complete eradication of tumors, depending on the in vitro immunogenicity of the inoculated multiple myeloma cells.CONCLUSIONS: Our results indicate that this new model allows convenient and sensitive real-time monitoring of cellular approaches for immunotherapy of multiple myeloma-like tumors with different immunogenicities. This model, therefore, allows comprehensive preclinical evaluation of novel combination therapies for multiple myeloma. |
| Databáze: | OpenAIRE |
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