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

被引：44

作者：

Tam, Eric M. ^{[1
]}

Fulton, Ross B. ^{[1
]}

Sampson, James F. ^{[1
]}

Muda, Marco ^{[1
]}

Camblin, Adam ^{[1
]}

Richards, Jennifer ^{[1
]}

Koshkaryev, Alexander ^{[1
]}

Tang, Jian ^{[1
]}

Kurella, Vinodh ^{[1
]}

Jiao, Yang ^{[1
]}

Xu, Lihui ^{[1
]}

Zhang, Kathy ^{[1
]}

Kohli, Neeraj ^{[1
]}

Luus, Lia ^{[1
]}

Hutto, Elizabeth ^{[2
]}

Kumar, Sandeep ^{[1
]}

Lulo, James ^{[1
]}

Paragas, Violette ^{[1
]}

Wong, Christina ^{[1
]}

Suchy, James ^{[1
]}

Grabow, Stephanie ^{[1
]}

Dugast, Anne-Sophie ^{[1
]}

Zhang, Hong ^{[1
]}

Depis, Fabien ^{[1
]}

Feau, Sonia ^{[1
]}

Jakubowski, Aniela ^{[1
]}

Qiao, Wenlian ^{[1
]}

Craig, Galina ^{[1
]}

Razlog, Maja ^{[1
]}

Qiu, James ^{[1
]}

Zhou, Yu ^{[3
]}

Marks, James D. ^{[3
]}

Croft, Michael ^{[4
,5
]}

Drummond, Daryl C. ^{[1
]}

Raue, Andreas ^{[1
]}

机构：

[1] Merrimack Pharmaceut Inc, Cambridge, MA 02139 USA

[2] Histosci Res Labs, Mt Jackson, VA 22842 USA

[3] Univ Calif San Francisco, San Francisco, CA 94110 USA

[4] La Jolla Inst Immunol, La Jolla, CA 92037 USA

[5] Univ Calif San Diego, La Jolla, CA 92037 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2019年 / 11卷 / 512期

关键词：

TUMOR-NECROSIS-FACTOR; FC-GAMMA RECEPTORS; EXPRESSION; MOUSE; EFFECTOR; CANCER; COSTIMULATOR; ANTI-PD-L1; BLOCKADE; SURVIVAL;

D O I：

10.1126/scitranslmed.aax0720

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 (T-regs) in autoimmune diseases, the viability of TNFR2 as a target for cancer immunotherapy has been under-appreciated. Here, we show that new murine monoclonal anti-TNFR2 antibodies yield robust antitumor activity and durable protective memory inmultiplemouse cancer cell linemodels. The antibodies mediate potent Fc-dependent T cell costimulation and do not result in significant depletion of T-regs. Corresponding human agonistic monoclonal anti-TNFR2 antibodies were identified and also had antitumor effects in humanized mousemodels. Anti-TNFR2 antibodies could be developed as a novel treatment option for patients with cancer.

引用

页数：15

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