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.

中文翻译：

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新型抗 GARP 抗体 DS-1055a 通过消耗高度抑制性 GARP+ 调节性 T 细胞增强抗肿瘤免疫力

调节性 T (Treg) 细胞对维持自身耐受至关重要，它抑制抗肿瘤免疫，从而阻碍保护性癌症免疫监视，并阻碍荷瘤宿主的有效抗肿瘤免疫反应。在这里，我们表明通过靶向糖蛋白 A 重复优势 (GARP) 来消耗 Treg 细胞可诱导有效的抗肿瘤免疫反应。GARP 由人类多种癌症类型的肿瘤微环境 (TME) 中的高度抑制性 Treg 细胞特异性表达。在外围，通过多克隆刺激，GARP 在 Treg 细胞中被选择性诱导，但在效应 T 细胞中不被诱导。DS-1055a，一种新型非岩藻糖基化抗人 GARP 单克隆抗体，可有效去除 GARP ⁺Treg 细胞，导致效应 T 细胞的激活。此外，DS-1055a 降低了 TME 中的 FoxP3 ⁺ CD4 ⁺ T 细胞，并在携带 HT-29 肿瘤的人源化小鼠中表现出显着的抗肿瘤活性。我们提出 DS-1055a 是一种新的 Treg 细胞靶向癌症免疫治疗剂，可增强抗肿瘤免疫力。