Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28951885
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Mol+Ther+Oncolytics
2017 ; 7
(ä): 1-11
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Cowpox Virus: A New and Armed Oncolytic Poxvirus
#MMPMID28951885
Ricordel M
; Foloppe J
; Pichon C
; Sfrontato N
; Antoine D
; Tosch C
; Cochin S
; Cordier P
; Quemeneur E
; Camus-Bouclainville C
; Bertagnoli S
; Erbs P
Mol Ther Oncolytics
2017[Dec]; 7
(ä): 1-11
PMID28951885
show ga
Oncolytic virus therapy has recently been recognized as a promising new
therapeutic approach for cancer treatment. In this study, we are proposing for
the first time to evaluate the in vitro and in vivo oncolytic capacities of the
Cowpox virus (CPXV). To improve the tumor selectivity and oncolytic activity, we
developed a thymidine kinase (TK)-deleted CPXV expressing the suicide gene FCU1,
which converts the non-toxic prodrug 5-fluorocytosine (5-FC) into cytotoxic
5-fluorouracil (5-FU) and 5-fluorouridine-5'-monophosphate (5-FUMP). This
TK-deleted virus replicated efficiently in human tumor cell lines; however, it
was notably attenuated in normal primary cells, thus displaying a good
therapeutic index. Furthermore, this new recombinant poxvirus rendered cells
sensitive to 5-FC. In vivo, after systemic injection in mice, the TK-deleted
variant caused significantly less mortality than the wild-type strain. A
biodistribution study demonstrated high tumor selectivity and low accumulation in
normal tissues. In human xenograft models of solid tumors, the recombinant CPXV
also displayed high replication, inducing relevant tumor growth inhibition. This
anti-tumor effect was improved by 5-FC co-administration. These results
demonstrated that CPXV is a promising oncolytic vector capable of expressing
functional therapeutic transgenes.
free
free
free
