TY - CHAP
T1 - Retroviral replicating vectors in cancer
AU - Logg, Christopher R.
AU - Robbins, Joan M.
AU - Jolly, Douglas J.
AU - Gruber, Harry E.
AU - Kasahara, Noriyuki
N1 - Funding Information:
This work was supported in part by Tocagen Inc., NIH grants R01 CA121258 and U01 NS059821 (to N.K.), and a pilot project grant from the UCLA CURE Digestive Disease Research Center (to C.R.L.). We would like to acknowledge the UCLA Vector Core & Shared Resource facility for their assistance with vector construction and characterization. Tocagen has also received support for this work from Accelerate Brain Cancer Cure (ABC 2 ) Foundation, Washington DC.
PY - 2012
Y1 - 2012
N2 - The use of replication-competent viruses for the treatment of cancer is an emerging technology that shows significant promise. Among the various different types of viruses currently being developed as oncolytic agents, retroviral replicating vectors (RRVs) possess unique characteristics that allow highly efficient, non-lytic, and tumor-selective gene transfer. By retaining all of the elements necessary for viral replication, RRVs are capable of transmitting genes via exponential in situ amplification. Their replication-competence also provides a powerful means whereby novel and useful RRV variants can be generated using natural selection. Their stringent requirement for cell division in order to achieve productive infection, and their preferential replication in cells with defective innate immunity, confer a considerable degree of natural specificity for tumors. Furthermore, their ability to integrate stably into the genome of cancer cells, without immediate cytolysis, contributes to long-lasting therapeutic efficacy. Thus, RRVs show much promise as therapeutic agents for cancer and are currently being tested in the clinic. Here we describe experimental methods for their production and quantitation, for adaptive evolution and natural selection to develop novel or improved RRV, and for in vitro and in vivo assessment of the therapeutic efficacy of RRVs carrying prodrug activator genes for treatment of cancer.
AB - The use of replication-competent viruses for the treatment of cancer is an emerging technology that shows significant promise. Among the various different types of viruses currently being developed as oncolytic agents, retroviral replicating vectors (RRVs) possess unique characteristics that allow highly efficient, non-lytic, and tumor-selective gene transfer. By retaining all of the elements necessary for viral replication, RRVs are capable of transmitting genes via exponential in situ amplification. Their replication-competence also provides a powerful means whereby novel and useful RRV variants can be generated using natural selection. Their stringent requirement for cell division in order to achieve productive infection, and their preferential replication in cells with defective innate immunity, confer a considerable degree of natural specificity for tumors. Furthermore, their ability to integrate stably into the genome of cancer cells, without immediate cytolysis, contributes to long-lasting therapeutic efficacy. Thus, RRVs show much promise as therapeutic agents for cancer and are currently being tested in the clinic. Here we describe experimental methods for their production and quantitation, for adaptive evolution and natural selection to develop novel or improved RRV, and for in vitro and in vivo assessment of the therapeutic efficacy of RRVs carrying prodrug activator genes for treatment of cancer.
KW - Glioblastoma
KW - Oncolytic virotherapy
KW - Prodrug activator gene therapy
KW - Replicating virus vector
KW - Replication-competent retrovirus
KW - Suicide gene therapy
UR - http://www.scopus.com/inward/record.url?scp=84857599195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857599195&partnerID=8YFLogxK
U2 - 10.1016/B978-0-12-386509-0.00011-9
DO - 10.1016/B978-0-12-386509-0.00011-9
M3 - Chapter
C2 - 22365776
AN - SCOPUS:84857599195
T3 - Methods in Enzymology
SP - 199
EP - 228
BT - Methods in Enzymology
PB - Academic Press Inc.
ER -