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Oncoimmunology. 2017 Nov 9;7(2):e1385690. doi: 10.1080/2162402X.2017.1385690. eCollection 2018.

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

Author information

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.

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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