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.
Stephanie Schwartz  1 ,  Nidhi Patel  1 ,  Tyler Longmire  1 ,  Pushpa Jayaraman  1 ,  Xiaomo Jiang  1 ,  Hongbo Lu  1 ,  Lisa Baker  1 ,  Janelle Velez  1 ,  Radha Ramesh  1 ,  Anne-Sophie Wavreille  2 ,  Melanie Verneret  2 ,  Hong Fan  3 ,  Tiancen Hu  3 ,  Fangmin Xu  4 ,  John Taraszka  4 ,  Marc Pelletier  5 ,  Joy Miyashiro  1 ,  Mikael Rinne  6 ,  Glenn Dranoff  1 ,  Catherine Sabatos-Peyton  1 ,  Viviana Cremasco  1
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.
PMID: 36196369 DOI: 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.

Products