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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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Detalles Bibliográficos
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
Descripción
Sumario: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.