期刊
INTERNATIONAL IMMUNOLOGY
卷 33, 期 8, 页码 435-446出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxab027
关键词
PD-1 blockade; cancer immunotherapy; immune modulation; immune suppression; regulatory T (Treg) cell
类别
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [17H06162, 16K15551]
- Projects for Cancer Research by Therapeutic Evolution [P-CREATE] [16cm0106301h0001]
- Japan Agency for Medical Research and Development (AMED) [19ae0101074s0401]
- National Cancer Center Research and Development Fund [28-A-7, 31-A-7]
- Daiichi Sankyo Co., Ltd.
- Grants-in-Aid for Scientific Research [17H06162, 16K15551] Funding Source: KAKEN
Regulatory T (Treg) cells play a crucial role in maintaining self-tolerance but can inhibit anti-tumor immunity, hindering effective immune responses against cancer. Targeting glycoprotein A repetitions predominant (GARP) can deplete Treg cells and activate effector T cells, showing potential for enhancing anti-tumor immunity in cancer immunotherapy.
Regulatory 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.
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