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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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.
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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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