Stephanie Schwartz, Nidhi Patel, Tyler Longmire, Pushpa Jayaraman, Xiaomo Jiang, Hongbo Lu, Lisa Baker, Janelle Velez, Radha Ramesh, Anne-Sophie Wavreille, Melanie Verneret, Hong Fan, Tiancen Hu, Fangmin Xu, John Taraszka, Marc Pelletier, Joy Miyashiro, Mikael Rinne, Glenn Dranoff, Catherine Sabatos-Peyton, Viviana Cremasco
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引用次数: 16
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.