The bispecific antibody HB-32, blockade of both VEGF and DLL4 shows potent anti-angiogenic activity in vitro and anti-tumor activity in breast cancer xenograft models
The bispecific antibody HB-32, blockade of both VEGF and DLL4 shows potent anti-angiogenic activity in vitro and anti-tumor activity in breast cancer xenograft models
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双特异性抗体 HB-32 可同时阻断 VEGF 和 DLL4，在体外显示出有效的抗血管生成活性，在乳腺癌异种移植模型中显示出有效的抗肿瘤活性
DOI：
10.1016/j.yexcr.2019.04.025
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发表时间：
2019
影响因子：
3.7
通讯作者：
Wu Min
中科院分区：
文献类型：
--
作者：
Zhou Rihong;Wang Shijing;Wen Hui;Wang Min;Wu Min
越来越多的临床前和临床研究表明，许多肿瘤模型对抗vegf - a和抗vegf - r2治疗具有耐药性。研究表明，同时阻断DLL4-Notch和VEGF信号通路，可协同抑制肿瘤血管密度和功能，降低肿瘤生长速度。我们成功开发了一种针对人DLL4和人VEGF的双特异性单克隆抗体（命名为HB-32）。HB-32对VEGF和DLL4具有较高的结合亲和力。HB-32还能抑制HUVEC的增殖、迁移和成管。最后，在体内异种移植研究表明，HB-32抑制乳腺癌细胞（MDA-MB-231）的增殖和诱导肿瘤细胞凋亡比单独抗vegf抗体或抗dll4抗体更有效。这些发现表明我们的双特异性抗体为乳腺癌提供了一种潜在的治疗方法。
Increasing preclinical and clinical studies revealed that many tumor models had resistance toanti-VEGF-A andanti-VEGF-R2 therapies. Studies have shown that simultaneously blocked DLL4-Notch and VEGF signaling pathways can synergistically inhibit density and function of tumor blood vessels and reduce tumor growth rate. We successfully developed a bispecific monoclonal antibody (named HB-32) that targeting both human DLL4 and human VEGF. HB-32 showed high binding affinity to VEGF and DLL4. Furthermore, HB-32 inhibited proliferation, migration and tube formation of HUVEC. Finally,in vivoxenograft studies demonstrated that HB-32 inhibited proliferation of breast cancer cells (MDA-MB-231) and induced tumor cell apoptosis more efficiently than ananti-VEGF antibody oranti-DLL4 antibody alone. These findings indicate that our bispecific antibody provide a potential treatment for breast cancer.