Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Oncoimmunology, 2018-02, Vol.7 (2), p.e1385690-e1385690

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• 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.