Avid Bioservices Inc (CDMO)

[hutschi]

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

Sabatos-Peyton CA1, Nevin J2, Brock A3, Venable JD3, Tan DJ2, Kassam N2, Xu F4, Taraszka J4, Wesemann L2, Pertel T2, Acharya N2, Klapholz M2, Etminan Y2, Jiang X1, Huang YH5, Blumberg RS5, Kuchroo VK2, Anderson AC2.

Author information

1Exploratory Immuno-oncology, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA, USA.Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.Department of Biotherapeutics and Biotechnology, Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Dr., San Diego, CA, USA.Analytical Sciences, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA.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.

https://www.ncbi.nlm.nih.gov/pubmed/29308307