2-fluorofucose (2FF) inhibits protein and cellular fucosylation. Afucosylation of IgG antibodies enhances antibody-dependent cell-mediated cytotoxicity by modulating antibody affinity for FcγRIIIa, which can impact secondary T-cell activation. Immune responses toward most common solid tumors are dominated by a humoral immune response rather than the presence of tumor-infiltrating cytotoxic T cells. IgG antibodies directed against numerous tumor-associated proteins are found in the sera of both patients with breast cancer and transgenic mice bearing mammary cancer. We questioned whether 2FF would have antitumor activity in two genetically distinct transgenic models; TgMMTV-neu (luminal B) and C3(1)-Tag (basal) mammary cancer. 2FF treatment significantly improved overall survival. The TgMMTV-neu doubled survival time compared with controls [P < 0.0001; HR, 7.04; 95% confidence interval (CI), 3.31–15.0], and survival was significantly improved in C3(1)-Tag (P = 0.0013; HR, 3.36; 95% CI, 1.58–7.14). 2FF treated mice, not controls, developed delayed-type hypersensitivity and T-cell responses specific for syngeneic tumor lysates (P < 0.0001). Serum IgG from 2FF-treated mice enhanced tumor lysis more efficiently than control sera (P = 0.004). Administration of 2FF for prophylaxis, at two different doses, significantly delayed tumor onset in both TgMMTV-neu; 20 mmol/L (P = 0.0004; HR, 3.55; 95% CI, 1.60–7.88) and 50 mmol/L (P = 0.0002; HR: 3.89; 95% CI, 1.71–8.86) and C3(1)-Tag; 20 mmol/L (P = 0.0020; HR, 2.51; 95% CI, 1.22–5.18), and 50 mmol/L (P = 0.0012; HR, 3.36; 95% CI, 1.57–7.18). Mammary cancer was prevented in 33% of TgMMTV-neu and 26% of C3(1)-Tag. 2FF has potent antitumor effects in mammary cancer models. The agent shows preclinical efficacy for both cancer treatment and prevention.

中文翻译：

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口服岩藻糖基化抑制剂在自发性乳腺癌中的治疗和预防性抗肿瘤活性

2-氟岩藻糖 (2FF) 抑制蛋白质和细胞岩藻糖基化。IgG 抗体的无岩藻糖基化通过调节抗体对 FcγRIIIa 的亲和力来增强抗体依赖性细胞介导的细胞毒性，这会影响二次 T 细胞活化。对大多数常见实体瘤的免疫反应主要是体液免疫反应，而不是肿瘤浸润性细胞毒性 T 细胞的存在。在乳腺癌患者和患有乳腺癌的转基因小鼠的血清中都发现了针对多种肿瘤相关蛋白的 IgG 抗体。我们质疑 2FF 在两种基因不同的转基因模型中是否具有抗肿瘤活性；TgMMTV-neu（管腔 B）和 C3(1)-Tag（基底）乳腺癌。2FF 治疗显着提高了总体生存率。与对照组相比，TgMMTV-neu 的存活时间翻了一番 [P < 0。0001; 人力资源，7.04；95% 置信区间 (CI)，3.31–15.0]，C3(1)-Tag 的存活率显着提高（P = 0.0013；HR，3.36；95% CI，1.58–7.14）。2FF 治疗的小鼠，而不是对照组，产生了对同源肿瘤裂解物特异的迟发型超敏反应和 T 细胞反应（P < 0.0001）。来自 2FF 处理小鼠的血清 IgG 比对照血清更有效地增强了肿瘤溶解（P = 0.004）。两种不同剂量的 2FF 用于预防，显着延迟了 TgMMTV-neu 中的肿瘤发作；20 mmol/L（P = 0.0004；HR，3.55；95% CI，1.60–7.88）和 50 mmol/L（P = 0.0002；HR：3.89；95% CI，1.71–8.86）和 C3(1)-Tag ; 20 mmol/L（P = 0.0020；HR，2.51；95% CI，1.22–5.18）和 50 mmol/L（P = 0.0012；HR，3.36；95% CI，1.57–7.18）。33% 的 TgMMTV-neu 和 26% 的 C3(1)-Tag 预防了乳腺癌。2FF 在乳腺癌模型中具有强大的抗肿瘤作用。该试剂显示出对癌症治疗和预防的临床前功效。