HER2 and VEGF are closely related to the progression of several tumors. The inhibitor simultaneously targeting these two proteins will effectively inhibit the progression of tumors. Here, a bispecific antibody, termed as YY0411, targeting both HER2 and VEGF as a potent anticancer therapeutic antibody is reported. YY0411 is the first bispecific antibody constructed in IgG‐Decoy receptor format. It efficiently identifies and combines both HER2 and VEGF protein. YY0411 is believed to be a candidate tumor suppressor as it significantly inhibits the colony formation ability of human cancer cells (Calu‐3, MDA‐MB‐453, and NCI‐N87 cells). The phosphorylation of HER2 and VEGF downstream components are also decreased in these cells with the treatment of YY0411. Similar to other antibodies, YY0411 has the ability to promote the secretion of IFN‐γ by T lymphocytes. In addition, YY0411 significantly inhibits the growth of Calu‐3 cells‐induced xenograft in nude mice. This work demonstrates that YY0411 may be a potential anti‐lung cancer drug.

中文翻译：

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构建新型双特异性抗体以增强抗肺癌的抗肿瘤活性。

HER2和VEGF与多种肿瘤的进展密切相关。同时针对这两种蛋白的抑制剂将有效抑制肿瘤的进展。在此，报道了一种名为 YY0411 的双特异性抗体，它同时靶向 HER2 和 VEGF，是一种有效的抗癌治疗抗体。YY0411是第一个以IgG-Decoy受体形式构建的双特异性抗体。它能有效识别并结合 HER2 和 VEGF 蛋白。YY0411 被认为是候选肿瘤抑制剂，因为它显着抑制人类癌细胞（Calu-3、MDA-MB-453 和 NCI-N87 细胞）的集落形成能力。YY0411 处理后，这些细胞中 HER2 和 VEGF 下游成分的磷酸化也有所降低。与其他抗体类似，YY0411具有促进T淋巴细胞分泌IFN-γ的能力。此外，YY0411 显着抑制 Calu-3 细胞诱导的裸鼠异种移植物的生长。这项工作表明YY0411可能是一种潜在的抗肺癌药物。