文章：

抗血管内皮生长因子B抗体可减少异常肿瘤血管并增强化疗效果

An Anti-VEGF-B Antibody Reduces Abnormal Tumor Vasculature and Enhances the Effects of Chemotherapy

原文发布日期：16 May 2024

DOI: 10.3390/cancers16101902

类型: Article

开放获取: 是

英文摘要：

The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key regulators of blood vessel formation, including in tumors, where their deregulated function can promote the production of aberrant, leaky blood vessels, supporting tumor development. Here we investigated the VEGFR1 ligand VEGF-B, which we demonstrate to be expressed in tumor cells and in tumor stroma and vasculature across a range of tumor types. We examined the anti-VEGF-B-specific monoclonal antibody 2H10 in preclinical xenograft models of breast and colorectal cancer, in comparison with the anti-VEGF-A antibody bevacizumab. Similar to bevacizumab, 2H10 therapy was associated with changes in tumor blood vessels and intra-tumoral diffusion consistent with normalization of the tumor vasculature. Accordingly, treatment resulted in partial inhibition of tumor growth, and significantly improved the response to chemotherapy. Our studies indicate the importance of VEGF-B in tumor growth, and the potential of specific anti-VEGF-B treatment to inhibit tumor development, alone or in combination with established chemotherapies.

摘要翻译： 

血管内皮生长因子（VEGFs）及其受体（VEGFRs）是血管生成的关键调节因子，在肿瘤中其功能失调可促进异常渗漏血管的生成，从而支持肿瘤发展。本研究聚焦于VEGFR1配体VEGF-B，我们证实该因子在多种肿瘤类型的肿瘤细胞、肿瘤基质及脉管系统中均有表达。通过乳腺癌和结直肠癌的临床前异种移植模型，我们评估了抗VEGF-B特异性单克隆抗体2H10的疗效，并与抗VEGF-A抗体贝伐珠单抗进行对比。与贝伐珠单抗类似，2H10治疗可引起肿瘤血管结构改变及瘤内扩散增强，这些变化与肿瘤血管正常化特征一致。该治疗能部分抑制肿瘤生长，并显著增强化疗药物的疗效。本研究揭示了VEGF-B在肿瘤生长中的重要作用，并证明特异性抗VEGF-B治疗单独或联合现有化疗方案均具有抑制肿瘤发展的潜力。

原文链接：

An Anti-VEGF-B Antibody Reduces Abnormal Tumor Vasculature and Enhances the Effects of Chemotherapy