PlGF阻塞不会在初级瘤生长过程中抑制血管生成
Carlos Bais1, Xiumin Wu, Jenny Yao
1Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. bais@gene.com
Cell
|April 8, 2010
概括
抗胎盘生长因子 (PlGF) 抗体在大多数模型中没有抑制瘤生长,尽管影响了伤口愈合. 临床使用抗PlGF疗法可能面临挑战.
科学领域:
- 瘤学 在瘤学方面.
- 癌症生物学 癌症生物学
- 免疫疗法是一种免疫疗法.
背景情况:
- 胎盘生长因子 (PlGF) 和它的受体VEGFR-1与瘤生长和转移有关.
- 在临床前研究中,抗PlGF抗体疗法已显示出抑制瘤进展的潜力.
研究的目的:
- 研究plgf在瘤血管生成和生长中的作用.
- 在临床前癌症模型中评估单独和与抗VEGF-A结合的抗PlGF抗体的疗效.
主要方法:
- 使用四种新型阻断抗体中和plgf.
- 对VEGFR-1的铁氨酸激酶域的基因切除.
- 在15个不同的模型中评估瘤血管生成,转移和原发性瘤生长.
- 用抗PlGF和抗VEGF-A抗体进行组合治疗.
主要成果:
- 反PlGF治疗抑制了伤口愈合和B16F10细胞扩散,但在15个模型中没有显著影响瘤血管生成.
- 基因移除VEGFR-1并没有抑制测试瘤的生长.
- 与抗PlGF和抗VEGF-A抗体的联合治疗与抗VEGF-A单一治疗相比没有表现出更高的抗瘤疗效.
结论:
- 在大多数测试模型中,plGF在原发性瘤生长中没有显著的作用.
- 抗PlGF抗体在癌症治疗中的临床效用可能有限.
- 需要进一步的研究来了解PLGF和VEGFR-1在癌症进展中的复杂作用.
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