Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor
Stephanie Schwartz, Nidhi Patel, Tyler A. Longmire, Pushpa Jayaraman, Xiaomo Jiang, Hongbo Lu, Lisa Baker, Janelle Velez, Radha Ramesh, Anne‐Sophie Wavreille, Mélanie Verneret, Hong Fan, Tiancen Hu, Fangmin Xu, John A. Taraszka, Marc R. Pelletier, Joy Miyashiro, Mikael L. Rinne, Glenn Dranoff, Catherine Sabatos-Peyton, Viviana Cremasco
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.