Norman Bethune College of Medicine, Jilin University, Changchun 130021, P.R. China.
Int J Oncol. 2013 Feb;42(2):507-16. doi: 10.3892/ijo.2012.1747. Epub 2012 Dec 20.
The anti‑erbB2 scFv‑Fc‑IL‑2 fusion protein (HFI) is the basis for development of a novel targeted anticancer drug, in particular for the treatment of HER2‑positive cancer patients. HFI was fused with the anti‑erbB2 antibody and human IL‑2 by genetic engineering technology and by antibody targeting characteristics of HFI. IL‑2 was recruited to target cells to block HER2 signaling, inhibit or kill tumor cells, improve the immune capacity, reduce the dose of antibody and IL‑2 synergy. In order to analyse HFI drug ability, HFI plasmid stability was verified by HFI expression of the trend of volume changes. Additionally, HFI could easily precipitate and had progressive characteristics and thus, the buffer system of the additive phosphate‑citric acid buffer, arginine, Triton X‑100 or Tween‑80, the establishment of a microfiltration, ion exchange, affinity chromatography and gel filtration chromatography‑based purification process were explored. HFI samples were obtained according to the requirements of purity, activity and homogeneity. In vivo, HFI significantly delayed HER2 overexpression of non‑small cell lung cancer (Calu‑3) in human non‑small cell lung cancer xenografts in nude mice, and the inhibition rate was more than 60% (P<0.05) in the group treated with 1 mg/kg the HFI dose; HFI significantly inhibited HER2 expression of breast cancer (FVB/neu) transgenic mouse tumor growth in 1 mg/kg of the HFI dose group, and in the following treatment the 400 mm3 tumors disappeared completely. Combined with other HFI test data analysis, HFI not only has good prospects, but also laid the foundation for the development of antibody‑cytokine fusion protein‑like drugs.
抗 erbB2 scFv-Fc-IL-2 融合蛋白（HFI）是开发新型靶向抗癌药物的基础，特别是用于治疗 HER2 阳性癌症患者。HFI 通过基因工程技术与抗 erbB2 抗体和人 IL-2 融合，并通过 HFI 的抗体靶向特性进行靶向。IL-2 被招募到靶细胞以阻断 HER2 信号，抑制或杀死肿瘤细胞，提高免疫能力，减少抗体和 IL-2 的协同作用。为了分析 HFI 的药物能力，通过 HFI 表达量的体积变化趋势验证了 HFI 质粒的稳定性。此外，HFI 容易沉淀且具有渐进性特征，因此，探索了添加磷酸盐-柠檬酸缓冲液、精氨酸、Triton X-100 或 Tween-80 的缓冲系统，建立了基于微滤、离子交换、亲和层析和凝胶过滤层析的纯化工艺。根据纯度、活性和均一性的要求获得 HFI 样品。在体内，HFI 显著延迟了人非小细胞肺癌裸鼠异种移植中 HER2 过表达的非小细胞肺癌（Calu-3），在 1mg/kg 的 HFI 剂量组中抑制率超过 60%（P<0.05）；HFI 显著抑制了 HER2 表达的乳腺癌（FVB/neu）转基因小鼠肿瘤生长，在 1mg/kg 的 HFI 剂量组中，400mm3 的肿瘤完全消失。结合其他 HFI 测试数据分析，HFI 不仅前景良好，而且为抗体-细胞因子融合蛋白样药物的开发奠定了基础。
