Ectodomain Antibody Fused to Trimeric Form of Adenovirus Receptor B-2 Oncoprotein by Single-Chain erb Adenovirus Targeting to c-Updated Version
Ectodomain Antibody Fused to Trimeric Form of Adenovirus Receptor B-2 Oncoprotein by Single-Chain erb Adenovirus Targeting to c-Updated Version
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通过单链 erb 腺病毒靶向 c 更新版本，将胞外域抗体与腺病毒受体 B-2 癌蛋白三聚体融合
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
I. Dmitriev
中科院分区：
文献类型：
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作者：
E. Kashentseva;T. Seki;D. Curiel;I. Dmitriev
腺病毒（Ad）载体用于癌症基因治疗应用的用途目前受到几个因素的限制，包括与正常人组织中柯萨奇病毒和腺病毒受体（CAR）的广泛表达相关的广泛Ad向性，以及肿瘤细胞中CAR的有限水平。为了将Ad靶向相关细胞类型，我们已经提出使用与配体融合的可溶性CAR（sCAR）胞外域来阻断CAR依赖性天然向性，并同时通过在靶细胞中过表达的新型受体实现感染。为了赋予Ad对表达c-erbB-2/HER-2/neu癌基因的癌细胞的靶向能力，我们设计了双特异性衔接蛋白sCARfC6.5，其由sCAR、噬菌体T4纤维蛋白多肽和针对c-erbB-2癌蛋白的C6.5单链可变片段（scFv）组成。纤维蛋白多肽的掺入提供了sCAR融合蛋白的三聚化，与单体sCAR蛋白相比，其导致对Ad纤维结结构域的亲和力增强和阻断CAR依赖性Ad感染的能力增加。我们证明了sCARfC6.5蛋白与细胞c-erbB-2癌蛋白结合，并通过CAR非依赖性途径介导有效的Ad靶向。如在过表达c-erbB-2的癌细胞系中所示，与sCARfC6.5衔接蛋白复合的靶向Ad与单独Ad相比提供1.5至17倍的基因转移增强，与与sCARf对照蛋白复合的非靶向Ad相比增加高达130倍。使用重组三聚体sCAR-scFv衔接子蛋白可以增强Ad载体靶向癌细胞类型的效力。
The use of adenovirus (Ad) vectors for cancer gene therapy applications is currently limited by several factors, including broad Ad tropism associated with the widespread expression of coxsackievirus and adenovirus receptor (CAR) in normal human tissues, as well as limited levels of CAR in tumor cells. To target Ad to relevant cell types, we have proposed using soluble CAR (sCAR) ectodomain fused with a ligand to block CARdependent native tropism and to simultaneously achieve infection through a novel receptor overexpressed in target cells. To confer Ad targeting capability on cancer cells expressing the c-erbB-2/HER-2/neu oncogene, we engineered a bispecific adapter protein, sCARfC6.5, that consisted of sCAR, phage T4 fibritin polypeptide, and C6.5 single-chain fragment variable (scFv) against c-erbB-2 oncoprotein. Incorporation of fibritin polypeptide provided trimerization of sCAR fusion proteins that, compared with monomeric sCAR protein, resulted in augmented affinity to Ad fiber knob domain and in increased ability to block CAR-dependent Ad infection. We demonstrated that sCARfC6.5 protein binds to cellular c-erbB-2 oncoprotein and mediates efficient Ad targeting via a CARindependent pathway. As illustrated in cancer cell lines that overexpress c-erbB-2, targeted Ad, complexed with sCARfC6.5 adapter protein, provided from 1.5to 17-fold enhancement of gene transfer compared with Ad alone and up to 130-fold increase in comparison with untargeted Ad complexed with sCARf control protein. The use of recombinant trimeric sCAR-scFv adapter proteins may augment Ad vector potency for targeting cancer cell types.
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DOI：
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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：
56.9
作者：
Bewley, MC;Springer, K;Flanagan, JM
通讯作者：
Flanagan, JM
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
作者：
M. Hung;Y. Lau
通讯作者：
M. Hung;Y. Lau
柯萨奇病毒和腺病毒受体表达对人类前列腺癌基因治疗的双重影响。
影响因子：
11.2
作者：
Okegawa,T;Li,Y;Pong,RC;Bergelson,JM;Zhou,J;Hsieh,JT
通讯作者：
Hsieh,JT