Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model
| Autor: | Lars Ny, Elin M. V. Söderberg, Jonas Nilsson, Mattias F. Lindberg, Inge Marie Svane, Rikke Andersen, Henrik Jespersen, Lisa M. Nilsson, Marco Donia, Ulrich Keller |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Melanoma/immunology Skin Neoplasms medicine.medical_treatment T-Lymphocytes General Physics and Astronomy Immunotherapy Adoptive 0302 clinical medicine Neoplasm Metastasis lcsh:Science Melanoma Mice Knockout Multidisciplinary biology Interleukin Receptor Common gamma Subunit/genetics medicine.anatomical_structure Antibodies Monoclonal Humanized/therapeutic use 030220 oncology & carcinogenesis Monoclonal Antibody Interleukin Receptor Common gamma Subunit Interleukin-2/genetics Skin Neoplasms/immunology T cell Science Antineoplastic Agents Antibodies Monoclonal Humanized General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Immune system Lymphocytes Tumor-Infiltrating Cell Line Tumor medicine Animals Humans Lymphocytes Tumor-Infiltrating/immunology business.industry Antineoplastic Agents/therapeutic use General Chemistry Immunotherapy T-Lymphocytes/immunology biochemical phenomena metabolism and nutrition medicine.disease 030104 developmental biology Immunology Humanized mouse biology.protein Interleukin-2 lcsh:Q business |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-10 (2017) Nature Communications Jespersen, H, Lindberg, M F, Donia, M, Söderberg, E M V, Andersen, R, Keller, U, Ny, L, Svane, I M, Nilsson, L M & Nilsson, J A 2017, ' Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model ', Nature Communications, vol. 8, 707 . https://doi.org/10.1038/s41467-017-00786-z |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-017-00786-z |
| Popis: | Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 — a melanoma PDX model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2). Tumors that grow in PDXv2.0 are eradicated if the autologous tumor cells and T cells come from a patient that exhibited an objective response to ACT in the clinic. However, T cells from patients that are non-responders to ACT cannot kill tumor cells in PDXv2.0. Taken together, PDXv2.0 provides the potential framework to further model genetically diverse human cancers for assessing the efficacy of immunotherapies as well as combination therapies. Combining different types of immune therapies might benefit certain patients. Here, the authors develop an autologous immune-humanized melanoma mouse model that allows the preclinical assessment of cancer cell–T cell interactions from each individual patient and the benefits of immunotherapies combinations. |
| Databáze: | OpenAIRE |
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