CD40-targeted adenoviral gene transfer to dendritic cells through the use of a novel bispecific single-chain Fv antibody enhances cytotoxic T cell activation

被引:49
作者
Brandao, JG
Scheper, RJ
Lougheed, SM
Curiel, DT
Tillman, BW
Gerritsen, WR
van den Eertwegh, AJM
Pinedo, HM
Haisma, HJ
de Gruijl, TD
机构
[1] VU Univ, Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Div Gene Therapy, Amsterdam, Netherlands
[3] Univ Alabama, Div Human Gene Therapy, Gene Therapy Ctr, Dept Med, Birmingham, AL USA
[4] Univ Alabama, Div Human Gene Therapy, Gene Therapy Ctr, Dept Pathol, Birmingham, AL USA
[5] Univ Alabama, Div Human Gene Therapy, Gene Therapy Ctr, Dept Surg, Birmingham, AL USA
[6] Univ Groningen, Ctr Pharm, Dept Therapeut Gene Modulat, Groningen, Netherlands
关键词
adenoviral; transduction; dendritic cells;
D O I
10.1016/S0264-410X(03)00050-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2268 / 2272
页数:5
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