Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor

Abstract 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 b... Mehr ...

Verfasser: 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
Dokumenttyp: Artikel
Erscheinungsdatum: 2022
Reihe/Periodikum: Immunotherapy Advances ; volume 2, issue 1 ; ISSN 2732-4303
Verlag/Hrsg.: Oxford University Press (OUP)
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27670664
Datenquelle: BASE; Originalkatalog
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Link(s) : http://dx.doi.org/10.1093/immadv/ltac019

Abstract 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.