Antibody-mediated targeting of TNFR2 activates CD8+ T cells in mice and promotes antitumor immunity.

Abstract

Tumor necrosis factor receptor 2 (TNFR2) is the alternate receptor for TNF and can mediate both pro- and anti-inflammatory activities of T cells. Although TNFR2 has been linked to enhanced suppressive activity of regulatory T cells (Tregs) in autoimmune diseases, the viability of TNFR2 as a target for cancer immunotherapy has been underappreciated. Here, we show that new murine monoclonal anti-TNFR2 antibodies yield robust antitumor activity and durable protective memory in multiple mouse cancer cell line models. The antibodies mediate potent Fc-dependent T cell costimulation and do not result in significant depletion of Tregs Corresponding human agonistic monoclonal anti-TNFR2 antibodies were identified and also had antitumor effects in humanized mouse models. Anti-TNFR2 antibodies could be developed as a novel treatment option for patients with cancer.

• Authors: Eric M Tam, Ross B Fulton, James F Sampson, Marco Muda, Adam Camblin, Jennifer Richards, Alexander Koshkaryev, Jian Tang, Vinodh Kurella, Yang Jiao, Lihui Xu, Kathy Zhang, Neeraj Kohli, Lia Luus, Elizabeth Hutto, Sandeep Kumar, James Lulo, Violette Paragas, Christina Wong, James Suchy, Stephanie Grabow, Anne-Sophie Dugast, Hong Zhang, Fabien Depis, Sonia Feau, Aniela Jakubowski, Wenlian Qiao, Galina Craig, Maja Razlog, James Qiu, Yu Zhou, James D Marks, Michael Croft, Daryl C Drummond, Andreas Raue
• Journal: Science translational medicine (Sci Transl Med) Vol. 11 Issue 512 (10 02 2019) ISSN: 1946-6242 [Electronic] United States
• PMID: 31578241 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Antibodies, Monoclonal
• Receptors, Tumor Necrosis Factor, Type II

Topics

• Animals
• Antibodies, Monoclonal (immunology, therapeutic use)
• CD8-Positive T-Lymphocytes (drug effects, metabolism)
• Colonic Neoplasms (immunology, metabolism, therapy)
• Disease Models, Animal
• Female
• Humans
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Receptors, Tumor Necrosis Factor, Type II (antagonists & inhibitors, immunology)