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Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor
OBJECTIVES: Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development and characterization of sabatolimab. METHODS: Sabatolimab was tested for binding to its target TIM-3 and block...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525012/ https://www.ncbi.nlm.nih.gov/pubmed/36196369 http://dx.doi.org/10.1093/immadv/ltac019 |
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author | Schwartz, Stephanie Patel, Nidhi Longmire, Tyler Jayaraman, Pushpa Jiang, Xiaomo Lu, Hongbo Baker, Lisa Velez, Janelle Ramesh, Radha Wavreille, Anne-Sophie Verneret, Melanie Fan, Hong Hu, Tiancen Xu, Fangmin Taraszka, John Pelletier, Marc Miyashiro, Joy Rinne, Mikael Dranoff, Glenn Sabatos-Peyton, Catherine Cremasco, Viviana |
author_facet | Schwartz, Stephanie Patel, Nidhi Longmire, Tyler Jayaraman, Pushpa Jiang, Xiaomo Lu, Hongbo Baker, Lisa Velez, Janelle Ramesh, Radha Wavreille, Anne-Sophie Verneret, Melanie Fan, Hong Hu, Tiancen Xu, Fangmin Taraszka, John Pelletier, Marc Miyashiro, Joy Rinne, Mikael Dranoff, Glenn Sabatos-Peyton, Catherine Cremasco, Viviana |
author_sort | Schwartz, Stephanie |
collection | PubMed |
description | OBJECTIVES: Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development and characterization of sabatolimab. METHODS: Sabatolimab was tested for binding to its target TIM-3 and blocking properties. The functional effects of sabatolimab were tested in T-cell killing and myeloid cell cytokine assays. Antibody-mediated cell phagocytosis (ADCP) by sabatolimab was also assessed. RESULTS: Sabatolimab was shown to (i) enhance T-cell killing and inflammatory cytokine production by dendritic cells (DCs); (ii) facilitate the phagocytic uptake of TIM-3-expressing target cells; and (iii) block the interaction between TIM-3 and its ligands PtdSer/galectin-9. CONCLUSION: Taken together, our results support both direct anti-leukemic effects and immune-mediated modulation by sabatolimab, reinforcing the notion that sabatolimab represents a novel immunotherapy with immuno-myeloid activity, holding promise for the treatment of myeloid cell neoplasms. |
format | Online Article Text |
id | pubmed-9525012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-95250122022-10-03 Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor Schwartz, Stephanie Patel, Nidhi Longmire, Tyler Jayaraman, Pushpa Jiang, Xiaomo Lu, Hongbo Baker, Lisa Velez, Janelle Ramesh, Radha Wavreille, Anne-Sophie Verneret, Melanie Fan, Hong Hu, Tiancen Xu, Fangmin Taraszka, John Pelletier, Marc Miyashiro, Joy Rinne, Mikael Dranoff, Glenn Sabatos-Peyton, Catherine Cremasco, Viviana Immunother Adv Research Article OBJECTIVES: Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development and characterization of sabatolimab. METHODS: Sabatolimab was tested for binding to its target TIM-3 and blocking properties. The functional effects of sabatolimab were tested in T-cell killing and myeloid cell cytokine assays. Antibody-mediated cell phagocytosis (ADCP) by sabatolimab was also assessed. RESULTS: Sabatolimab was shown to (i) enhance T-cell killing and inflammatory cytokine production by dendritic cells (DCs); (ii) facilitate the phagocytic uptake of TIM-3-expressing target cells; and (iii) block the interaction between TIM-3 and its ligands PtdSer/galectin-9. CONCLUSION: Taken together, our results support both direct anti-leukemic effects and immune-mediated modulation by sabatolimab, reinforcing the notion that sabatolimab represents a novel immunotherapy with immuno-myeloid activity, holding promise for the treatment of myeloid cell neoplasms. Oxford University Press 2022-08-10 /pmc/articles/PMC9525012/ /pubmed/36196369 http://dx.doi.org/10.1093/immadv/ltac019 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Schwartz, Stephanie Patel, Nidhi Longmire, Tyler Jayaraman, Pushpa Jiang, Xiaomo Lu, Hongbo Baker, Lisa Velez, Janelle Ramesh, Radha Wavreille, Anne-Sophie Verneret, Melanie Fan, Hong Hu, Tiancen Xu, Fangmin Taraszka, John Pelletier, Marc Miyashiro, Joy Rinne, Mikael Dranoff, Glenn Sabatos-Peyton, Catherine Cremasco, Viviana Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor |
title | Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor |
title_full | Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor |
title_fullStr | Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor |
title_full_unstemmed | Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor |
title_short | Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor |
title_sort | characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against tim-3 receptor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525012/ https://www.ncbi.nlm.nih.gov/pubmed/36196369 http://dx.doi.org/10.1093/immadv/ltac019 |
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