The purpose of this study is to assess the safety and tolerability of DS-1055a in participants with relapsed or refractory locally advanced or metastatic solid tumors for which no standard treatment is available.

Start Date09 Oct 2020

Sponsor / Collaborator

Daiichi Sankyo Co., Ltd.

100 Clinical Results associated with DS-1055

100 Translational Medicine associated with DS-1055

100 Patents (Medical) associated with DS-1055

Literatures (Medical) associated with DS-1055

23 Jul 2021·International ImmunologyQ3 · MEDICINE

Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells

Q3 · MEDICINE

Article

Author: Tuettenberg, Andrea ; Sugiyama, Daisuke ; Hata, Masato ; Hayashi, Shinko ; Satoh, Kazuki ; Nishikawa, Hiroyoshi ; Hirahara, Kazuki ; Agatsuma, Toshinori ; Ishida, Saori ; Sato, Takahiko ; Jonuleit, Helmut ; Kozuma, Shiho ; Wakita, Kenichi ; Fujimaki, Kaori ; Maruyama, Shoichi ; Amano, Masato ; Okamoto, Atsushi ; Wada, Teiji ; Watanabe, Ichiro ; Lim, Kyungtaek ; Kobayashi, Yoichi ; Tanemura, Atsushi ; Miyamoto, Megumi ; Kadokura, Michinori

AbstractRegulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor 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 anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.

100 Deals associated with DS-1055

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 1	CA	Daiichi Sankyo Co., Ltd.	09 Oct 2020
Advanced cancer	Phase 1	US	Daiichi Sankyo Co., Ltd.	09 Oct 2020
Advanced cancer	Phase 1	JP	Daiichi Sankyo Co., Ltd.	09 Oct 2020
Metastatic Solid Tumor	Phase 1	CA	Daiichi Sankyo Co., Ltd.	09 Oct 2020
Metastatic Solid Tumor	Phase 1	US	Daiichi Sankyo Co., Ltd.	09 Oct 2020
Metastatic Solid Tumor	Phase 1	JP	Daiichi Sankyo Co., Ltd.	09 Oct 2020

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