Targeting of adenovirus to endothelial cells by a bispecific single-chain diabody directed against the adenovirus fiber knob domain and human endoglin (CD105).
Targeting of adenovirus to endothelial cells by a bispecific single-chain diabody directed against the adenovirus fiber knob domain and human endoglin (CD105).
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通过针对腺病毒纤维旋钮结构域和人内皮糖蛋白 (CD105) 的双特异性单链双抗体将腺病毒靶向内皮细胞。
作者：
D. Nettelbeck;Daniel Miller;V. Jérôme;Marylou Zuzarte;Sarah J. Watkins;R. Hawkins;R. Müller;R. Kontermann
腺病毒用于抗血管癌基因治疗的用途因其对内皮细胞的转导效率低而受到限制。我们开发了一种重组双特异性抗体作为分子桥，将腺病毒衣壳与内皮细胞表面蛋白内皮糖蛋白连接起来，用于腺病毒的血管靶向。内皮糖蛋白 (CD105) 是转化生长因子 β 受体复合物的一个组成部分，是抗血管癌治疗的一个有前景的靶点。内皮糖蛋白主要在内皮细胞上表达，并在肿瘤的血管生成区域上调。我们从人半合成抗体库中分离出针对人内皮糖蛋白的单链 Fv 片段。分离的 scFv 片段之一 (scFv C4) 特异性结合各种增殖的原代内皮细胞或细胞系，包括 HUVEC、HDMEC、HMVEC 和 HMEC。因此，ScFv C4 用于构建针对内皮糖蛋白和腺病毒纤维旋钮结构域（scDb EDG-Ad）的双特异性单链双抗体。这种双特异性分子介导 HUVEC 的增强和选择性腺病毒转导，其独立于柯萨奇病毒和腺病毒受体 (CAR) 和 α(v)-整合素的结合。因此，腺病毒感染被重定向到新的细胞受体（CD105）和细胞进入途径。这些结果证明了双特异性单链双抗体的实用性，该双特异性单链双抗体可以在细菌中大量产生，用于癌症基因治疗中腺病毒的重新靶向。
The use of adenoviruses for antivascular cancer gene therapy is limited by their low transduction efficiency for endothelial cells. We have developed a recombinant bispecific antibody as a molecular bridge, linking the adenovirus capsid to the endothelial cell surface protein endoglin, for vascular targeting of adenoviruses. Endoglin (CD105), a component of the transforming growth factor beta receptor complex, represents a promising target for antivascular cancer therapy. Endoglin is expressed predominantly on endothelial cells and is upregulated in angiogenic areas of tumors. We isolated single-chain Fv fragments directed against human endoglin from a human semisynthetic antibody library. One of the isolated scFv fragments (scFv C4) bound specifically to various proliferating primary endothelial cells or cell lines including HUVEC, HDMEC, HMVEC, and HMEC. ScFv C4 was therefore used to construct a bispecific single-chain diabody directed against endoglin and the adenovirus fiber knob domain (scDb EDG-Ad). This bispecific molecule mediated enhanced and selective adenovirus transduction of HUVECs, which was independent from binding to the coxsackievirus and adenovirus receptor (CAR) and alpha(v)-integrins. Thus, adenovirus infection was redirected to a new cellular receptor (CD105) and cell entry pathway. These results demonstrate the utility of bispecific single-chain diabodies, which can be produced in large quantities in bacteria, for the retargeting of adenoviruses in cancer gene therapy.
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影响因子：
21.1
作者：
A. Griffioen;G. Molema
通讯作者：
A. Griffioen;G. Molema
DOI：
--
发表时间：
1998-10
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Claudine Rancourt;Buck E. Rogers;B. Sosnowski;M. Wang;Alain Piché;G. Pierce;R. Alvarez;Gene P. Siegal;J. T. Douglas;David T. Curiel
通讯作者：
Claudine Rancourt;Buck E. Rogers;B. Sosnowski;M. Wang;Alain Piché;G. Pierce;R. Alvarez;Gene P. Siegal;J. T. Douglas;David T. Curiel
影响因子：
5
作者：
Ando M;Nagata K;Nihira K;Suzuki Y;Kanda Y;Adachi M;Kubota T;Kameyama N;Nakano M;Ando H;Yamano K;Ishii T;Nakai R;Nakamura K
通讯作者：
Nakamura K
影响因子：
4.4
作者：
O. Rokhlin;M. Cohen;H. Kubagawa;M. Letarte;M. Cooper
通讯作者：
O. Rokhlin;M. Cohen;H. Kubagawa;M. Letarte;M. Cooper
DOI：
--
发表时间：
1999-02
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
F. Matsuno;Y. Haruta;M. Kondo;H. Tsai;M. Barcos;B. Seon
通讯作者：
F. Matsuno;Y. Haruta;M. Kondo;H. Tsai;M. Barcos;B. Seon