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

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

doi:10.1093/immadv/ltac019

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

Immunother Adv. 2022 Aug 10;2(1):ltac019. doi: 10.1093/immadv/ltac019. eCollection 2022.

Authors

Stephanie Schwartz¹, Nidhi Patel¹, Tyler Longmire¹, Pushpa Jayaraman¹, Xiaomo Jiang¹, Hongbo Lu¹, Lisa Baker¹, Janelle Velez¹, Radha Ramesh¹, Anne-Sophie Wavreille², Melanie Verneret², Hong Fan³, Tiancen Hu³, Fangmin Xu⁴, John Taraszka⁴, Marc Pelletier⁵, Joy Miyashiro¹, Mikael Rinne⁶, Glenn Dranoff¹, Catherine Sabatos-Peyton¹, Viviana Cremasco¹

Affiliations

¹ Immuno-Oncology and Hematology, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
² Technical R&D GDD, Novartis Pharma Services AG., Basel, Switzerland.
³ Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
⁴ Biotherapeutic and Analytical Technologies, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
⁵ Oncology Translational Research, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
⁶ Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

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.