Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro
Antibodies are commonly used in organ transplant induction therapy and to treat autoimmune disorders. The effects of some biologics on the human immune system remain incompletely characterized and a deeper understanding of their mechanisms of action may provide useful insights for their clinical app...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.592553/full |
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| author | Christian Binder Christian Binder Felix Sellberg Felix Sellberg Filip Cvetkovski Erik Berglund Erik Berglund David Berglund David Berglund |
| author_facet | Christian Binder Christian Binder Felix Sellberg Felix Sellberg Filip Cvetkovski Erik Berglund Erik Berglund David Berglund David Berglund |
| author_sort | Christian Binder |
| collection | DOAJ |
| description | Antibodies are commonly used in organ transplant induction therapy and to treat autoimmune disorders. The effects of some biologics on the human immune system remain incompletely characterized and a deeper understanding of their mechanisms of action may provide useful insights for their clinical application. The goal of this study was to contrast the mechanistic properties of siplizumab with Alemtuzumab and rabbit Anti-Thymocyte Globulin (rATG). Mechanistic assay systems investigating antibody-dependent cell-mediated cytotoxicity, antibody-dependent cell phagocytosis and complement-dependent cytotoxicity were used to characterize siplizumab. Further, functional effects of siplizumab, Alemtuzumab, and rATG were investigated in allogeneic mixed lymphocyte reaction. Changes in T cell activation, T cell proliferation and frequency of naïve T cells, memory T cells and regulatory T cells induced by siplizumab, Alemtuzumab and rATG in allogeneic mixed lymphocyte reaction were assessed via flow cytometry. Siplizumab depleted T cells, decreased T cell activation, inhibited T cell proliferation and enriched naïve and bona fide regulatory T cells. Neither Alemtuzumab nor rATG induced the same combination of functional effects. The results presented in this study should be used for further in vitro and in vivo investigations that guide the clinical use of immune modulatory biologics. |
| first_indexed | 2024-12-19T14:43:13Z |
| format | Article |
| id | doaj.art-b5441494d1094b3ba95b51413da6001a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T14:43:13Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b5441494d1094b3ba95b51413da6001a2022-12-21T20:17:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.592553592553Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In VitroChristian Binder0Christian Binder1Felix Sellberg2Felix Sellberg3Filip Cvetkovski4Erik Berglund5Erik Berglund6David Berglund7David Berglund8Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenResearch and Development, ITB-Med AB, Stockholm, SwedenSection of Clinical Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenResearch and Development, ITB-Med AB, Stockholm, SwedenResearch and Development, ITB-Med AB, Stockholm, SwedenResearch and Development, ITB-Med AB, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology (CLINTEC), Division of Transplantation Surgery, Karolinska Institute and Karolinska University Hospital, Stockholm, SwedenSection of Clinical Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenResearch and Development, ITB-Med AB, Stockholm, SwedenAntibodies are commonly used in organ transplant induction therapy and to treat autoimmune disorders. The effects of some biologics on the human immune system remain incompletely characterized and a deeper understanding of their mechanisms of action may provide useful insights for their clinical application. The goal of this study was to contrast the mechanistic properties of siplizumab with Alemtuzumab and rabbit Anti-Thymocyte Globulin (rATG). Mechanistic assay systems investigating antibody-dependent cell-mediated cytotoxicity, antibody-dependent cell phagocytosis and complement-dependent cytotoxicity were used to characterize siplizumab. Further, functional effects of siplizumab, Alemtuzumab, and rATG were investigated in allogeneic mixed lymphocyte reaction. Changes in T cell activation, T cell proliferation and frequency of naïve T cells, memory T cells and regulatory T cells induced by siplizumab, Alemtuzumab and rATG in allogeneic mixed lymphocyte reaction were assessed via flow cytometry. Siplizumab depleted T cells, decreased T cell activation, inhibited T cell proliferation and enriched naïve and bona fide regulatory T cells. Neither Alemtuzumab nor rATG induced the same combination of functional effects. The results presented in this study should be used for further in vitro and in vivo investigations that guide the clinical use of immune modulatory biologics.https://www.frontiersin.org/articles/10.3389/fimmu.2020.592553/fullsiplizumabT cell biologyimmunotherapycostimulation blockadeimmune modulation |
| spellingShingle | Christian Binder Christian Binder Felix Sellberg Felix Sellberg Filip Cvetkovski Erik Berglund Erik Berglund David Berglund David Berglund Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro Frontiers in Immunology siplizumab T cell biology immunotherapy costimulation blockade immune modulation |
| title | Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro |
| title_full | Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro |
| title_fullStr | Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro |
| title_full_unstemmed | Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro |
| title_short | Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin In Vitro |
| title_sort | siplizumab an anti cd2 monoclonal antibody induces a unique set of immune modulatory effects compared to alemtuzumab and rabbit anti thymocyte globulin in vitro |
| topic | siplizumab T cell biology immunotherapy costimulation blockade immune modulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.592553/full |
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