Agonistic nanobodies and antibodies to human VISTA
The V-domain Ig Suppressor of T-cell Activation (VISTA) is an immune checkpoint regulator that suppresses immune responses and is readily expressed on human and murine myeloid cells and T cells. This immunosuppressive pathway can be activated using VISTA agonists. Here, we report the development of...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2021.2003281 |
| _version_ | 1798040840981970944 |
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| author | Yu-Heng Vivian Ma Amanda Sparkes Ema Romão Shrayasee Saha Jean Gariépy |
| author_facet | Yu-Heng Vivian Ma Amanda Sparkes Ema Romão Shrayasee Saha Jean Gariépy |
| author_sort | Yu-Heng Vivian Ma |
| collection | DOAJ |
| description | The V-domain Ig Suppressor of T-cell Activation (VISTA) is an immune checkpoint regulator that suppresses immune responses and is readily expressed on human and murine myeloid cells and T cells. This immunosuppressive pathway can be activated using VISTA agonists. Here, we report the development of murine anti-human VISTA (anti-hVISTA) monoclonal antibodies (mAbs), anti-hVISTA nanobodies (Nbs), and cross-reactive rat anti-murine/human VISTA (anti-hmVISTA) mAbs. All mAbs and Nbs generated bound to VISTA (human and/or murine) with dissociation constants in the sub-nanomolar or low nanomolar range. Competition analysis revealed that the selected Nbs bound the same or a nearby epitope(s) as the human VISTA-specific mAbs. However, the cross-reactive mAbs only partially competed with Nbs for binding to hVISTA. All mAbs and one Nb (hVISTANb7) were able to strongly detect VISTA expression on primary human monocytes. Importantly, the murine anti-hVISTA mAbs 7E12 and 7G5 displayed strong agonistic activity in human peripheral blood mononuclear cell cultures, while Nb7 and rat anti-hmVISTA mAbs 3C3, 7C6, 7C7, and 7G1 also behaved as hVISTA agonists, albeit to a lesser extent. Cross-reactive mAbs 7C7 and 7G1 further displayed agonistic potential in murine splenocyte assays. Importantly, mAb 7G1 significantly reduced inflammation associated with the murine model of imiquimod-induced psoriasis. These agonistic VISTA mAbs may represent therapeutic leads to treat inflammatory disorders. |
| first_indexed | 2024-04-11T22:13:13Z |
| format | Article |
| id | doaj.art-f59647e7b99f4f21a7e6a706007da58e |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2024-04-11T22:13:13Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-f59647e7b99f4f21a7e6a706007da58e2022-12-22T04:00:31ZengTaylor & Francis GroupmAbs1942-08621942-08702021-01-0113110.1080/19420862.2021.2003281Agonistic nanobodies and antibodies to human VISTAYu-Heng Vivian Ma0Amanda Sparkes1Ema Romão2Shrayasee Saha3Jean Gariépy4Physical Sciences, Sunnybrook Research Institute, Toronto, CanadaPhysical Sciences, Sunnybrook Research Institute, Toronto, CanadaCellular and Molecular Immunology Lab, Vrije Universiteit Brussel, Ixelles, BelgiumDepartment of Pharmaceutical Sciences, University of Toronto, Toronto, CanadaPhysical Sciences, Sunnybrook Research Institute, Toronto, CanadaThe V-domain Ig Suppressor of T-cell Activation (VISTA) is an immune checkpoint regulator that suppresses immune responses and is readily expressed on human and murine myeloid cells and T cells. This immunosuppressive pathway can be activated using VISTA agonists. Here, we report the development of murine anti-human VISTA (anti-hVISTA) monoclonal antibodies (mAbs), anti-hVISTA nanobodies (Nbs), and cross-reactive rat anti-murine/human VISTA (anti-hmVISTA) mAbs. All mAbs and Nbs generated bound to VISTA (human and/or murine) with dissociation constants in the sub-nanomolar or low nanomolar range. Competition analysis revealed that the selected Nbs bound the same or a nearby epitope(s) as the human VISTA-specific mAbs. However, the cross-reactive mAbs only partially competed with Nbs for binding to hVISTA. All mAbs and one Nb (hVISTANb7) were able to strongly detect VISTA expression on primary human monocytes. Importantly, the murine anti-hVISTA mAbs 7E12 and 7G5 displayed strong agonistic activity in human peripheral blood mononuclear cell cultures, while Nb7 and rat anti-hmVISTA mAbs 3C3, 7C6, 7C7, and 7G1 also behaved as hVISTA agonists, albeit to a lesser extent. Cross-reactive mAbs 7C7 and 7G1 further displayed agonistic potential in murine splenocyte assays. Importantly, mAb 7G1 significantly reduced inflammation associated with the murine model of imiquimod-induced psoriasis. These agonistic VISTA mAbs may represent therapeutic leads to treat inflammatory disorders.https://www.tandfonline.com/doi/10.1080/19420862.2021.2003281VISTAmonoclonal antibodiesnanobodiesagonisticanti-inflammatorypsoriasis |
| spellingShingle | Yu-Heng Vivian Ma Amanda Sparkes Ema Romão Shrayasee Saha Jean Gariépy Agonistic nanobodies and antibodies to human VISTA mAbs VISTA monoclonal antibodies nanobodies agonistic anti-inflammatory psoriasis |
| title | Agonistic nanobodies and antibodies to human VISTA |
| title_full | Agonistic nanobodies and antibodies to human VISTA |
| title_fullStr | Agonistic nanobodies and antibodies to human VISTA |
| title_full_unstemmed | Agonistic nanobodies and antibodies to human VISTA |
| title_short | Agonistic nanobodies and antibodies to human VISTA |
| title_sort | agonistic nanobodies and antibodies to human vista |
| topic | VISTA monoclonal antibodies nanobodies agonistic anti-inflammatory psoriasis |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2021.2003281 |
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