An anti-human VEGF monoclonal antibody, MV833, that exhibits potent anti-tumor activity in vivo
An anti-human VEGF monoclonal antibody, MV833, that exhibits potent anti-tumor activity in vivo
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DOI：
10.1089/hyb.1998.17.185
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发表时间：
1998-04-01
期刊：
影响因子：
--
通讯作者：
Suzuki, H
中科院分区：
文献类型：
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作者：
Asano, M;Yukita, A;Suzuki, H
血管内皮生长因子（VEGF）是一种强有力的促血管生成因子，可促进肿瘤血管生成和生长。我们先前建立了抗人VEGF的免疫中和单克隆抗体（MAbs），并显示MV 101（IgG 1）和MV 303（IgG 2a）抑制裸鼠人实体瘤移植瘤的生长。然后，我们试图开发另一种免疫中和抗VEGF单克隆抗体，其表现出比MV 101或MV 303更强的抗肿瘤活性。我们从用重组人VEGF免疫的小鼠中获得了140多个产生抗VEGF单克隆抗体的杂交瘤克隆（121）。其中26个克隆具有免疫中和活性，MV 833具有最强的体内抗肿瘤活性。总共9次IP给予25 μ g MV 833比MV 101或MV 303更有效地抑制裸鼠中异种移植的人纤维肉瘤HT-1080实体瘤的生长。此外，在肿瘤接种后第1天仅1次IV给予100 μ g MV 833也显著抑制HT-1080的体内生长。3株单抗均能抑制VEGF（121）诱导的人脐静脉内皮细胞（HUVEC）生长，并能抑制I-125标记的VEGF（121）与HUVEC的结合。MV 101和MV 303与VEGF的结合是交叉竞争的（121）;然而，MV 833与MV 101与VEGF的结合弱竞争（121）。这些发现表明MV 833与MV 101或MV 303不同地识别VEGF的区域，并且这种差异有助于MV 833的抗肿瘤活性的优越性。
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor for tumor angiogenesis and growth. We previously established the immunoneutralizing monoclonal antibodies (MAbs) to human VEGF, and showed that MV101 (IgG1) and MV303 (IgG2a) inhibited the growth of human solid tumor xenografts in nude mice. Then, we tried to develop another immunoneutralizing anti-VEGF MAb that exhibited more potent antitumor activity than MV101 or MV303, We obtained more than 140 clones of hybridomas that were producing anti-VEGF MAb from the mice immunized with recombinant human VEGF(121). Among them, 26 clones showed the immunoneutralizing activity and MV833 possessed the most potent antitumor activity in vivo. A total of 9 IP administrations of 25 mu g of MV833 inhibited the growth of human fibrosarcoma HT-1080 solid tumor xenografted in nude mice more potently than MV101 or MV303, Moreover, only 1 IV administration of 100 mu g of MV833 on Day 1 after tumor inoculation also significantly inhibited the growth of HT-1080 in vivo, whereas MV101 and MV303 did not.All three MAbs inhibited the growth of human umbilical vein endothelial cells (HUVEC) induced by VEGF(121) and the binding of I-125-labeled VEGF(121) to HUVEC to a similar extent. The binding of MV101 and MV303 to VEGF(121) was cross-competitive; however, MV833 weakly competed with the binding of MV101 to VEGF(121), These findings indicated that MV833 recognized the region(s) of VEGF differently than MV101 or MV303, and this difference contributed to the superiority of antitumor activity of MV833.