2. Academic Validation
  3. Blockade of Tim-3 binding to phosphatidylserine and CEACAM1 is a shared feature of anti-Tim-3 antibodies that have functional efficacy

Blockade of Tim-3 binding to phosphatidylserine and CEACAM1 is a shared feature of anti-Tim-3 antibodies that have functional efficacy

  • Oncoimmunology. 2017 Nov 9;7(2):e1385690. doi: 10.1080/2162402X.2017.1385690.
Catherine A Sabatos-Peyton 1,  James Nevin 2,  Ansgar Brock 3,  John D Venable 3,  Dewar J Tan 2,  Nasim Kassam 2,  Fangmin Xu 4,  John Taraszka 4,  Luke Wesemann 2,  Thomas Pertel 2,  Nandini Acharya 2,  Max Klapholz 2,  Yassaman Etminan 2,  Xiaomo Jiang 1,  Yu-Hwa Huang 5,  Richard S Blumberg 5,  Vijay K Kuchroo 2,  Ana C Anderson 2
Affiliations

Affiliations

  • 1 Exploratory Immuno-oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, USA.
  • 2 Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • 3 Department of Biotherapeutics and Biotechnology, Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA, USA.
  • 4 Analytical Sciences, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA.
  • 5 Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
PMID: 29308307 DOI: 10.1080/2162402X.2017.1385690
Abstract

Both in vivo data in preclinical Cancer models and in vitro data with T cells from patients with advanced Cancer support a role for TIM-3 blockade in promoting effective anti-tumor immunity. Consequently, there is considerable interest in the clinical development of antibody-based therapeutics that target TIM-3 for Cancer Immunotherapy. A challenge to this clinical development is the fact that several ligands for TIM-3 have been identified: Galectin-9, phosphatidylserine, HMGB1, and most recently, CEACAM1. These observations raise the important question of which of these multiple receptor:ligand relationships must be blocked by an anti-Tim-3 antibody in order to achieve therapeutic efficacy. Here, we have examined the properties of anti-murine and anti-human TIM-3 antibodies that have shown functional efficacy and find that all antibodies bind to TIM-3 in a manner that interferes with TIM-3 binding to both phosphatidylserine and CEACAM1. Our data have implications for the understanding of TIM-3 biology and for the screening of anti-Tim-3 antibody candidates that will have functional properties in vivo.

Keywords

HDxMS; Tim-3; antibody; checkpoint receptor; ligand.

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