OncoImmunology (Feb 2018)

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

  • Catherine A. Sabatos-Peyton,
  • James Nevin,
  • Ansgar Brock,
  • John D. Venable,
  • Dewar J. Tan,
  • Nasim Kassam,
  • Fangmin Xu,
  • John Taraszka,
  • Luke Wesemann,
  • Thomas Pertel,
  • Nandini Acharya,
  • Max Klapholz,
  • Yassaman Etminan,
  • Xiaomo Jiang,
  • Yu-Hwa Huang,
  • Richard S. Blumberg,
  • Vijay K. Kuchroo,
  • Ana C. Anderson

DOI
https://doi.org/10.1080/2162402X.2017.1385690
Journal volume & issue
Vol. 7, no. 2

Abstract

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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.

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