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

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

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.

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