Mapping of angiogenic markers for targeting of vectors to tumor vascular endothelial cells
Mapping of angiogenic markers for targeting of vectors to tumor vascular endothelial cells
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DOI：
10.1038/sj.cgt.7701030
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发表时间：
2007-04-01
影响因子：
6.4
通讯作者：
Deisseroth, A.
中科院分区：
文献类型：
--
作者：
Tang, Y.;Borgstrom, P.;Deisseroth, A.
在活体显微镜（IVM）观察室中，生长在乳腺脂肪垫组织上的小鼠乳腺肿瘤球体的血管系统显示来自浸润性血管生成乳腺血管。受体组织因子（TF）、α V β 3整联蛋白和Tie-2在外周的血管内皮上表达，但在肿瘤球体的中心、乳腺组织和平滑肌组织中不表达，而Tie-1和PCAM-1在整个肿瘤和整个肿瘤结节的血管内皮以及正常乳腺组织中广泛表达。TF是腺病毒载体介导的肿瘤免疫治疗的特异性靶点。皮下注射AdfVII/IgG（1）Fc载体导致fVII/ IgG（1）Fc免疫缀合物分子释放到系统循环中，该分子特异性且紧密地结合血管内皮细胞和肿瘤细胞上的TF，激活针对靶细胞的溶细胞免疫应答。我们发现，单次给予AdfVII/ IgG（1）Fc载体可破坏肿瘤球体的外周血管，但不能破坏肿瘤球体的中央血管，导致部分肿瘤消退;额外给药可防止外周血管再生和肿瘤再生长。这些发现表明，优化肿瘤损伤的关键参数是AdfVII/ IgG（1）Fc连续给药的时间表，该时间表应与外周血管再生一致，并持续至肿瘤被破坏。Cancer Gene Therapy（2007）14，346-353. doi：10.1038/ sj.总表7701030; 2007年1月19日在线发布。
The vasculature of mouse breast tumor spheroids grown on mammary fat pad tissue in an intravital microscopy (IVM) viewing chamber was shown to derive from infiltrating angiogenic mammary vessels. The receptors tissue factor (TF), alpha V beta 3 integrin and Tie-2 were expressed on the vascular endothelium in the periphery but not in the center of the tumor spheroids nor in the mammary tissue nor in smooth muscle tissue, whereas Tie-1 and PCAM-1 were expressed extensively in the entire tumor and in the vascular endothelium of the entire tumor nodule and in normal mammary tissue. TF is a specific target for adenoviral vector-mediated cancer immunotherapy. Subcutaneous injection of the AdfVII/IgG(1)Fc vector leads to the release into the system circulation of a fVII/ IgG(1)Fc immunoconjugate molecule that binds specifically and tightly to TF on vascular endothelial cells and tumor cells, activating a cytolytic immune response against the targeted cells. We show that a single administration of the AdfVII/ IgG(1)Fc vector destroys the peripheral but not the central vasculature of a tumor spheroid, causing partial tumor regression; additional administrations prevent regeneration of the peripheral vasculature and regrowth of the tumor. These findings indicate that a critical parameter for optimizing tumor damage is the schedule for successive administrations of the AdfVII/ IgG(1)Fc, which should coincide with the regeneration of the peripheral vasculature and continue until the tumor is destroyed. Cancer Gene Therapy (2007) 14, 346-353. doi: 10.1038/ sj. cgt. 7701030; published online 19 January 2007.