Passive tumour targeting of polymer-coated adenovirus for cancer gene therapy.
Adenovirus provides many opportunities as a vector for delivery of cytotoxic genes to tumours. Polymer coating of adenovirus is known to increase its plasma circulation kinetics, affording the possibility of active and passive targeting to tumours. Here we show that polymer-coating adenovirus (pc-virus) abrogates its normal infectivity in vitro and also in liver following intravenous injection. The coated virus accumulates within solid subcutaneous AB22 mesothelioma tumours 40-times more than unmodified virus, and mediates higher levels of transgene expression within tumours. This is the first demonstration of passive tumour targeting of polymer-coated adenoviruses administered by intravenous injection, and also the first time pc-virus has been shown to be infectious following passive targeting to tumours in vivo. This technology provides an interesting option for delivery of therapeutic viruses to disseminated tumour masses by intravenous injection.
Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Oxford, UK.
Kerry D
KD
Fisher
Nicola K
NK
Green
Ashley
A
Hale
Vladimir
V
Subr
Karel
K
Ulbrich
Leonard W
LW
Seymour
D000256:Adenoviridae / Q000737:chemistry / Q000472:pathogenicity; D000818:Animals; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007275:Injections, Intravenous; D008654:Mesothelioma / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000628:therapy*; D050130:Oncolytic Virotherapy; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D019076:Transgenes
D011108:Polymers