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Journal of Virology, January 2001, p. 480-489, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.480-489.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Functional and Selective Targeting of Adenovirus to High-Affinity Fcgamma Receptor I-Positive Cells by Using a Bispecific Hybrid Adapter

Christina Ebbinghaus,1 Ahmed Al-Jaibaji,1 Elisabeth Operschall,2 Angelika Schöffel,1 Isabelle Peter,1 Urs F. Greber,3 and Silvio Hemmi1,*

Institute of Molecular Biology1 and Institute of Zoology,3 University of Zürich, CH-8057 Zürich, and Institute of Medical Virology, University of Zürich, CH-8028 Zürich,2 Switzerland

Received 1 June 2000/Accepted 29 September 2000

Adenovirus (Ad) efficiently delivers its DNA genome into a variety of cells and tissues, provided that these cells express appropriate receptors, including the coxsackie-adenovirus receptor (CAR), which binds to the terminal knob domain of the viral capsid protein fiber. To render CAR-negative cells susceptible to Ad infection, we have produced a bispecific hybrid adapter protein consisting of the amino-terminal extracellular domain of the human CAR protein (CARex) and the Fc region of the human immunoglobulin G1 protein, comprising the hinge and the CH2 and CH3 regions. CARex-Fc was purified from COS7 cell supernatants and mixed with Ad particles, thus blocking Ad infection of CAR-positive but Fc receptor-negative cells. The functionality of the CARex domain was further confirmed by successful immunization of mice with CARex-Fc followed by selection of a monoclonal anti-human CAR antibody (E1-1), which blocked Ad infection of CAR-positive cells. When mixed with Ad expressing eGFP, CARex-Fc mediated an up to 250-fold increase of transgene expression in CAR-negative human monocytic cell lines expressing the high-affinity Fcgamma receptor I (CD64) but not in cells expressing the low-affinity Fcgamma receptor II (CD32) or III (CD16). These results open new perspectives for Ad-mediated cancer cell vaccination, including the treatment of acute myeloid leukemia.

* Corresponding author. Mailing address: Institute of Molecular Biology, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland. Phone: 0041 1 635 3120. Fax: 0041 1 635 6864. E-mail: hemmi{at}molbio.unizh.ch.

Journal of Virology, January 2001, p. 480-489, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.480-489.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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