Authors: Satoh, Kazuki; Kobayashi, Yoichi; Fujimaki, Kaori; Hayashi, Shinko; Ishida, Saori; Sugiyama, Daisuke; Sato, Takahiko; Kyungtaek, Lim; Miyamoto, Megumi; Kozuma, Shiho; Kadokura, Michinori; Wakita, Kenichi; Hata, Masato; Hirahara, Kazuki; Amano, Masato; Watanabe, Ichiro; Okamoto, Atsushi; Tuettenberg, Andrea; Jonuleit, Helmut; Tanemura, Atsushi; Maruyama, Shoichi; Agatsuma, Toshinori; Wada, Teiji; Nishikawa, Hiroyoshi
Online: https://academic.oup.com/intimm/advance-article/doi/10.1093/intimm/dxab027/6291826
Issue: Int Immunol. 2021 Jul 23;33(8):435-446.
Abstract
Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit antitumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective antitumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective antitumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP + Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3 +CD4 + T cells in the TME and exhibited remarkable antitumor activity in a humanized mouse bearing HT29 tumor. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of antitumor immunity.
