Fermentation, Purification, and Tumor Inhibition of a Disulfide-Stabilized Diabody Against Fibroblast Growth Factor-2.
Fermentation, Purification, and Tumor Inhibition of a Disulfide-Stabilized Diabody Against Fibroblast Growth Factor-2.
复制标题
抗成纤维细胞生长因子-2的二硫键稳定的双抗体的发酵、纯化和肿瘤抑制。
DOI：
10.3389/fonc.2021.585457
复制
发表时间：
2021
影响因子：
4.7
通讯作者：
Deng N
中科院分区：
文献类型：
--
作者：
Zhang S;Huang J;Zhang L;Gu J;Song Q;Cai Y;Zhong J;Zhong H;Deng Y;Zhu W;Zhao J;Deng N
血管生成被认为是癌症的标志之一，在肿瘤的发展中起着至关重要的作用。成纤维细胞生长因子 2 (FGF-2) 是 FGF 家族的成员，参与癌细胞过度增殖和肿瘤血管生成。因此，靶向FGF-2被认为是一种有前途的抗肿瘤策略。在毕赤酵母（GS115）中通过发酵产生了针对FGF-2的二硫键稳定的双抗体（ds-Diabody），并分析了其抗肿瘤活性。采用新设计的培养基建立了新型10L补料分批发酵，抗FGF-2双链抗体的最大产量达到210.4mg/L。通过Ni2+亲和层析和DEAE阴离子交换层析纯化抗FGF-2的双链抗体。抗FGF-2的重组ds-Diabody可有效抑制FGF-2刺激的黑色素瘤和胶质瘤肿瘤细胞的增殖、迁移和侵袭。此外，异种移植肿瘤模型测定表明，针对 FGF-2 的 ds-Diabody 通过抑制肿瘤生长和血管生成，在裸鼠中具有有效的抗肿瘤活性。黑色素瘤和胶质瘤的肿瘤生长抑制率分别约为70%和45%。黑色素瘤和胶质瘤的肿瘤血管生成抑制率分别约为64%和51%。结果表明，针对FGF-2的重组双链抗体可能是一种有前途的癌症治疗抗肿瘤药物。
Angiogenesis is considered one of the hallmarks of cancer and plays a critical role in the development of tumor. Fibroblast growth factor 2 (FGF-2) is a member of the FGF family and participates in excessive cancer cell proliferation and tumor angiogenesis. Thus, targeting FGF-2 was considered to be a promising anti-tumor strategy. A disulfide-stabilized diabody (ds-Diabody) against FGF-2 was produced in Pichia pastoris (GS115) by fermentation and the anti-tumor activity was analyzed. The novel 10-L fed batch fermentation with newly designed media was established, and the maximum production of the ds-Diabody against FGF-2 reached 210.4 mg/L. The ds-Diabody against FGF-2 was purified by Ni2+ affinity chromatography and DEAE anion exchange chromatography. The recombinant ds-Diabody against FGF-2 could effectively inhibit proliferation, migration, and invasion of melanoma and glioma tumor cells stimulated by FGF-2. Furthermore, xenograft tumor model assays showed that the ds-Diabody against FGF-2 had potent antitumor activity in nude mice by inhibiting tumor growth and angiogenesis. The tumor growth inhibition rate of melanoma and glioma was about 70 and 45%, respectively. The tumor angiogenesis inhibition rate of melanoma and glioma was about 64 and 51%, respectively. The results revealed that the recombinant ds-Diabody against FGF-2 may be a promising anti-tumor drug for cancer therapy.
登录
查看更多内容
影响因子：
5.2
作者：
Rezzola, Sara;Ronca, Roberto;Presta, Marco
通讯作者：
Presta, Marco
影响因子：
3.3
作者：
Robinson, Emily S.;Khankin, Eliyahu V.;Karumanchi, S. Ananth;Humphreys, Benjamin D.
通讯作者：
Humphreys, Benjamin D.
FGF家族：从药物研发到临床应用
影响因子：
5.6
作者：
Hui Q;Jin Z;Li X;Liu C;Wang X
通讯作者：
Wang X
影响因子：
--
作者：
Akl MR;Nagpal P;Ayoub NM;Tai B;Prabhu SA;Capac CM;Gliksman M;Goy A;Suh KS
通讯作者：
Suh KS
影响因子：
2.6
作者：
Celik, Eda;Calik, Pinar;Oliver, Stephen G.
通讯作者：
Oliver, Stephen G.