Angiopoietin-2特定cvx - 060与化疗协同抑制肿瘤的生长

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黄H, J,李L,赖J,刘D, Pirie-Shepherd年代,莱文N,布拉德肖C, Woodnutt G, Lappe R, Bhat

Angiopoietin-2特定cvx - 060与化疗协同抑制肿瘤的生长

癌症研究》2008年5月1日,68 (9 _supplement): 2493。

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而(Ang-1)和Angiopoietin-2 (Ang-2)是内皮细胞受体的配体Tie2。Ang-1维持稳定的脉管系统是至关重要的。在重构内皮细胞,Ang-2作为内生Ang-1拮抗剂。Ang-2促进从现有血管周围的周的分离,并导致不稳定的血管,从而形成新的血管的增殖和扩散的VEGF。Ang-2表达在许多癌症与更多侵入性疾病,预后较差。特定Ang-2绑定CovX-BodyTM预计060年,是由融合化学改性药效团的工厂特别设计的抗体结合位点。预计060年封锁Ang-2-Tie2交互的IC50 1海里。的抗肿瘤活性cvx - 060在科罗拉多州举行评估- 205。显著减少观察肿瘤的生长(P < 0.01) [T / C(治疗/控制)= 53%)单药治疗。cvx - 060结合伊立替康或多烯紫杉醇生产更大的抑制肿瘤的生长(T / C ~ 50%至36%和31%,分别)和延迟时间达到一个预先确定的肿瘤体积(2000 mm3)相比,车辆控制和单药治疗组。 In fact, the combination groups never reached 2000 mm3 during the study. Ang2 protein levels examined by immunostaining were significantly reduced in CVX-060 treated tumors. Tumor microvessel density assessed by CD31 staining was also significantly reduced by ~33% (P < 0.01). Histological analysis revealed that CVX-060 increased tumor necrosis by 63% (P < 0.01). Tie2 expressing monocytes can be recruited into tumors and differentiate into pro-angiogenic macrophages. Tie2+ CD14+ or CD11b+ cell number examined by immunohistochemistry were reduced by 76% in CVX-060 treated tumors compared to the Vehicle group (P < 0.01). These data demonstrate that the Ang-2 CovX-BodyTM CVX-060 can effectively reduce Ang-2 protein level and Tie2+ macrophages inside the tumor mass, and inhibit tumor angiogenesis and growth. Significant combination benefit was also observed with other standard of care agents.

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