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Bispecific Adapter-Mediated Retargeting of a Receptor-Restricted HSV-1 Vector to CEA-Bearing Tumor Cells

Authors
Baek, HyunjungUchida, HiroakiJun, KyungokKim, Jae-HongKuroki, MasahideCohen, Justus B.Glorioso, Joseph C.Kwon, Heechung
Issue Date
3월-2011
Publisher
CELL PRESS
Citation
MOLECULAR THERAPY, v.19, no.3, pp.507 - 514
Indexed
SCIE
SCOPUS
Journal Title
MOLECULAR THERAPY
Volume
19
Number
3
Start Page
507
End Page
514
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/112881
DOI
10.1038/mt.2010.207
ISSN
1525-0016
Abstract
The safety and efficacy of viral therapies for solid tumors can be enhanced by redirecting the virus infection to tumor-specific cell-surface markers. Successful retargeting of herpes simplex virus type 1 (HSV-1) has been achieved using vectors that carry a modified envelope glycoprotein D (gD) engineered to interact directly with novel receptors. In addition, soluble bridging molecules (adapters) have been used to link gD indirectly to cellspecific receptors. Here, we describe the development of an adapter connecting gD to the common tumor antigen carcinoembryonic antigen (CEA). The adapter consisted of a CEA-specific single-chain antibody fused to the gD-binding region of the gD receptor, herpes virus entry mediator (HVEM). We used this adapter in combination with a vector that is detargeted for recognition of the widely expressed gD receptor nectin-1, but retains an intact binding region for the less common HVEM. We show that the adapter enabled infection of HSV-resistant Chinese hamster ovary (CHO) cells expressing ectopic CEA and nectin-1/CEA-bearing human gastric carcinoma cells that are resistant to the vector alone. We observed cell-to-cell spread following adapter-mediated infection in vitro and reduced tumor growth in vivo, indicating that this method of vector retargeting may provide a novel strategy for tumor-specific delivery of tumoricidal HSV.
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생명과학대학 (생명과학부)
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