A humanized CD3ε-knock-in mouse model for pre-clinical testing of anti-human CD3 therapy
| Autor: | Yi Ting Koh, Andrew L. Glasebrook, Ningjie Hu, Ezio Bonvini, Joel Crespo, Andrea P. Martin, Robert J. Benschop, Paul A. Moore |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
CD3 Complex
Physiology T-Lymphocytes Biochemistry White Blood Cells Mice Spectrum Analysis Techniques Animal Cells Immune Physiology Medicine and Health Sciences Medicine Cytotoxic T cell Gene Knock-In Techniques Immune Response Multidisciplinary Thymocytes Immune System Proteins biology Effector T Cells Stem Cells Antibodies Monoclonal Animal Models Flow Cytometry Thymocyte medicine.anatomical_structure Phenotype Experimental Organism Systems Spectrophotometry Cytophotometry Antibody Cellular Types Research Article Hematopoietic Progenitor Cells T cell CD3 Immune Cells Science Immunology Mouse Models Cytotoxic T cells Research and Analysis Methods Antibodies Immune system Model Organisms Antigen Animals Humans Blood Cells business.industry Biology and Life Sciences Proteins Cell Biology Mice Inbred C57BL biology.protein Animal Studies business Spleen |
| Zdroj: | PLoS ONE, Vol 16, Iss 2, p e0245917 (2021) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Pre-clinical murine models are critical for translating drug candidates from the bench to the bedside. There is interest in better understanding how anti-human CD3 therapy works based on recent longitudinal studies of short-term administration. Although several models have been created in this pursuit, each have their own advantages and disadvantages in Type-1 diabetes. In this study, we report a murine genetic knock-in model which expresses both a murine and a humanized-CD3ε-exon, rendering it sensitive to manipulation with anti-human CD3. These huCD3εHET mice are viable and display no gross abnormalities. Specifically, thymocyte development and T cell peripheral homeostasis is unaffected. We tested immune functionality of these mice by immunizing them with T cell-dependent antigens and no differences in antibody titers compared to wild type mice were recorded. Finally, we performed a graft-vs-host disease model that is driven by effector T cell responses and observed a wasting disease upon transfer of huCD3εHET T cells. Our results show a viable humanized CD3 murine model that develops normally, is functionally engaged by anti-human CD3 and can instruct on pre-clinical tests of anti-human CD3 antibodies. |
| Databáze: | OpenAIRE |
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