TY - JOUR
T1 - Oncolytic adenoviruses - Selective retargeting to tumor cells
AU - Mathis, J. Michael
AU - Stoff-Khalili, Mariam A.
AU - Curiel, David T.
N1 - Funding Information:
This work was supported by NIH grant P50 CA86306 and DOD award W81XWH-04-1-0025. We acknowledge support from the Louisiana Gene Therapy Research Consortium, Inc.
PY - 2005/11/21
Y1 - 2005/11/21
N2 - Virotherapy is an approach for the treatment of cancer, in which the replicating virus itself is the anticancer agent. Virotherapy exploits the lytic property of virus replication to kill tumor cells. As this approach relies on viral replication, the virus can self-amplify and spread in the tumor from an initial infection of only a few cells. The success of this approach is fundamentally based on the ability to deliver the replication-competent viral genome to target cells with a requisite level of efficiency. With virotherapy, while a number of transcriptional retargeting strategies have been utilized to restrict viral replication to tumor cells, this review will focus primarily on transductional retargeting strategies, whereby oncolytic viruses can be designed to selectively infect tumor cells. Using the adenoviral vector paradigm, there are three broad strategies useful for viral retargeting. One strategy uses heterologous retargeting ligands that are bispecific in that they bind both to the viral vector as well as to a cell surface target. A second strategy uses genetically modified viral vectors in which a cellular retargeting ligand is incorporated. A third strategy involves the construction of chimeric recombinant vectors, in which a capsid protein from one virus is exchanged for that of another. These transductional retargeting strategies have the potential for reducing deleterious side effects, and increasing the therapeutic index of virotherapeutic agents.
AB - Virotherapy is an approach for the treatment of cancer, in which the replicating virus itself is the anticancer agent. Virotherapy exploits the lytic property of virus replication to kill tumor cells. As this approach relies on viral replication, the virus can self-amplify and spread in the tumor from an initial infection of only a few cells. The success of this approach is fundamentally based on the ability to deliver the replication-competent viral genome to target cells with a requisite level of efficiency. With virotherapy, while a number of transcriptional retargeting strategies have been utilized to restrict viral replication to tumor cells, this review will focus primarily on transductional retargeting strategies, whereby oncolytic viruses can be designed to selectively infect tumor cells. Using the adenoviral vector paradigm, there are three broad strategies useful for viral retargeting. One strategy uses heterologous retargeting ligands that are bispecific in that they bind both to the viral vector as well as to a cell surface target. A second strategy uses genetically modified viral vectors in which a cellular retargeting ligand is incorporated. A third strategy involves the construction of chimeric recombinant vectors, in which a capsid protein from one virus is exchanged for that of another. These transductional retargeting strategies have the potential for reducing deleterious side effects, and increasing the therapeutic index of virotherapeutic agents.
UR - http://www.scopus.com/inward/record.url?scp=27944445010&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1209044
DO - 10.1038/sj.onc.1209044
M3 - Review article
C2 - 16299537
AN - SCOPUS:27944445010
SN - 0950-9232
VL - 24
SP - 7775
EP - 7791
JO - Oncogene
JF - Oncogene
IS - 52
ER -