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An immunocompetent mouse model of human glioblastoma

Orthotopic xenotransplantation studies represent the final stage in preclinical cancer research and could facilitate the implementation of precision medicine. To date, these xenografts have been tested in immunodeficient animals, but complete elimination of the adaptive immunity is a significant dra...

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Detalles Bibliográficos
Autores principales: Semenkow, Samantha, Li, Shen, Kahlert, Ulf D., Raabe, Eric H., Xu, Jiadi, Arnold, Antje, Janowski, Miroslaw, Oh, Byoung Chol, Brandacher, Gerald, Bulte, Jeff W.M., Eberhart, Charles G., Walczak, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617407/
https://www.ncbi.nlm.nih.gov/pubmed/28977847
http://dx.doi.org/10.18632/oncotarget.17851
Descripción
Sumario:Orthotopic xenotransplantation studies represent the final stage in preclinical cancer research and could facilitate the implementation of precision medicine. To date, these xenografts have been tested in immunodeficient animals, but complete elimination of the adaptive immunity is a significant drawback. We present a method of efficient human glioblastoma (GBM) cell engraftment in adult mice with intact immune systems, mediated by a transient blockade of T-cell co-stimulation. Compared to transplants grown in immunodeficient hosts, the resulting tumors more accurately resemble the clinical pathophysiology of patient GBMs, which are characterized by blood-brain-barrier leakage and strong neo-vascularization. We expect our method to have great utility for studying human tumor cell biology, particularly in the field of cancer immunotherapy and in studies on microenvironmental interactions. Given the straightforward approach, the method may also be applicable to other tumor types and additional model organisms.