CD40-targeted adenoviral gene transfer to dendritic cells through the use of a novel bispecific single-chain Fv antibody enhances cytotoxic T cell activation
CD40-targeted adenoviral gene transfer to dendritic cells through the use of a novel bispecific single-chain Fv antibody enhances cytotoxic T cell activation
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DOI：
10.1016/s0264-410x(03)00050-1
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发表时间：
2003-06-02
期刊：
影响因子：
5.5
通讯作者：
de Gruijl, TD
中科院分区：
文献类型：
--
作者：
Brandao, JG;Scheper, RJ;de Gruijl, TD
腺病毒（Ad）转导树突状细胞（DC）是一种很有前途的疫苗接种策略。然而，Ad载体的临床应用受到使用高滴度的感染性Ad颗粒用于有效DC转导的必要性的阻碍。在这里，我们报告了细菌表达的双特异性缀合物的产生，其由重组单链（sc）mAb Fv片段的融合物组成，其结合并中和Ad纤维球（通过S11 mAb scFv）并将Ad重靶向DC表面上的CD 40（通过G28-5 mAb scFv）。我们表明，这种双特异性scFv融合蛋白显着提高单核细胞来源的DC（MoDC）的转导效率，减少了给定水平的转导所需的病毒的量，并增加了MoDC以抗原特异性方式激活CTL的能力。这种单组分缀合物也可被证明是用于体内将Ad靶向DC的有价值的免疫剂。(C)2003爱思唯尔科技有限公司。保留所有权利。
Adenoviral (Ad) transduction of dendritic cells (DC) is a promising vaccination strategy. However, clinical applicability of Ad vectors is hampered by the necessity to use high titers of infectious Ad particles for efficient DC transduction. Here, we report on the production of a bacterially expressed bispecific conjugate, consisting of a fusion of recombinant single-chain (sc) mAb Fv fragments, which bind and neutralize the Ad fiber knob (through the S11 mAb scFv) and retarget Ad to CD40 on the DC surface (through the G28-5 mAb scFv). We show that this bispecific scFv fusion protein significantly enhances transduction efficiency of monocyte-derived DC (MoDC), reduces the amount of virus needed for a given level of transduction, and increases the ability of MoDC to activate CTL in an antigen specific manner. This single-component conjugate may prove to be a valuable immunotherapeutic too] for the targeting of Ad to DC in vivo. (C) 2003 Elsevier Science Ltd. All rights reserved.