Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor121.
Inhibition of tumor growth and metastasis by an immunoneutralizing monoclonal antibody to human vascular endothelial growth factor/vascular permeability factor121.
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通过针对人血管内皮生长因子/血管通透因子的免疫中和单克隆抗体抑制肿瘤生长和转移121。
作者：
M. Asano;A. Yukita;Tomoe Matsumoto;S. Kondo;Hideo Suzuki
我们阐明了血管内皮生长因子/血管通透性因子（VEGF/VPF），这是一种有效的血管生成因子，与原发性和转移性肿瘤的生长之间的关系，使用免疫中和单克隆抗体对人VEGF/VPF 121。单克隆抗体MV 303可抑制VEGF/VPF 121或VEGF/VPF 165诱导的人脐静脉内皮细胞（HUVEC）生长，但不抑制碱性成纤维细胞生长因子诱导的HUVEC生长。MV 303抑制125 I-VEGF/VPF 121与HUVEC的结合。我们使用填充有人纤维肉瘤细胞系HT-1080并皮下植入的膜室来检测MV 303对肿瘤血管生成的影响。BALB/c小鼠。通过静脉注射100微克/小鼠的剂量的MV 303抑制HT-1080诱导的新血管形成。此外，s.c.在BALB/c裸鼠中植入HT-1080几乎被i. v.和s.c.从第1天开始以100微克/小鼠的剂量施用MV 303十次（第18天肿瘤体积的T/C值分别为0.20和0.18）。当施用MV 303时，甚至从肿瘤接种后8天开始，肿瘤生长受到抑制。MV 303抑制了通过静脉接种培养的HT-1080细胞到BALB/c裸鼠的实验转移引起的肺重量增加。用MV 303处理的小鼠的寿命显著延长。这些结果表明，VEGF/VPF作为肿瘤血管生成因子在原发性和转移性肿瘤生长中起重要作用。MV 303是一种抗VEGF/VPF的免疫中和单克隆抗体，可有效抑制原发性和转移性肿瘤生长，无明显副作用。
We elucidated the relationship between vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), which is a potent angiogenic factor, and the growth of primary and metastatic tumors using an immunoneutralizing monoclonal antibody against human VEGF/VPF121. The monoclonal antibody, MV303, suppressed the growth of human umbilical vein endothelial cells (HUVEC) induced by VEGF/VPF121 or VEGF/VPF165 but did not inhibit its growth induced by basic fibroblast growth factor. MV303 inhibited the binding of 125I-VEGF/VPF121 to HUVEC. We examined the effects of MV303 on tumor angiogenesis using a membrane chamber packed with the human fibrosarcoma cell line HT-1080 and implanted s.c. into BALB/c mice. The neovascularization induced by HT-1080 was inhibited by the i.v. injection of MV303 at a dose of 100 micrograms/mouse. Furthermore, the growth of solid tumors of s.c. implanted HT-1080 in BALB/c nude mice was almost completely inhibited by the i.v. and s.c. administration of MV303 ten times from day 1 at a dose of 100 micrograms/mouse (T/C values of tumor volume at day 18 were 0.20 and 0.18, respectively). Tumor growth was suppressed when MV303 was administered, even from eight days after tumor inoculation. MV303 suppressed the increase in lung weight caused by experimental metastasis with i.v. inoculation of cultured HT-1080 cells to BALB/c nude mice. The life spans of the mice treated with MV303 were significantly prolonged. These results indicated that VEGF/VPF played an important role in both primary and metastatic tumor growth as a tumor angiogenesis factor. MV303, an immunoneutralizing monoclonal antibody against VEGF/VPF, potently inhibited both primary and metastatic tumor growth with no marked side effects.
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DOI：
10.1111/j.1349-7006.2002.tb01302.x
发表时间：
2002-06
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Akutagawa N;Nishikawa A;Iwasaki M;Fujimoto T;Teramoto M;Kitajima Y;Endo T;Shibuya M;Kudo R
通讯作者：
Kudo R
影响因子：
56.9
作者：
DEVRIES, C;ESCOBEDO, JA;WILLIAMS, LT
通讯作者：
WILLIAMS, LT
DOI：
10.1073/pnas.88.13.5819
发表时间：
1991-07-01
影响因子：
11.1
作者：
MYOKEN, Y;KAYADA, Y;SATO, JD
通讯作者：
SATO, JD
影响因子：
8
作者：
B. I. Terman;M. E. Carrion;E. Kovács;Rasmussen Ba;Eddy Rl;T. Shows
通讯作者：
B. I. Terman;M. E. Carrion;E. Kovács;Rasmussen Ba;Eddy Rl;T. Shows