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

Author:

Schwartz Stephanie1,Patel Nidhi1,Longmire Tyler1,Jayaraman Pushpa1,Jiang Xiaomo1,Lu Hongbo1,Baker Lisa1,Velez Janelle1,Ramesh Radha1,Wavreille Anne-Sophie2,Verneret Melanie2,Fan Hong3,Hu Tiancen3,Xu Fangmin4,Taraszka John4,Pelletier Marc5,Miyashiro Joy1,Rinne Mikael6,Dranoff Glenn1,Sabatos-Peyton Catherine1,Cremasco Viviana1ORCID

Affiliation:

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

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.

Publisher

Oxford University Press (OUP)

Subject

General Medicine

Reference41 articles.

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2. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1;Chiba;Nat Immunol,2012

3. T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells;DeKruyff;J Immunol,2010

4. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion;Huang;Nature,2015

5. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity;Zhu;Nat Immunol,2005

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