Production of an EGFR targeting molecule from a conditionally replicating adenovirus impairs its oncolytic potential.
Oncolytic virotherapy with conditionally replicating viruses is a promising approach for treating advanced cancers. Promiscuous tropism and low tumor transduction have represented limiting issues, which targeting approaches seek to overcome. An approach utilizing a secretory targeting molecule for the epidermal growth factor pathway (sCAR-EGF) has previously been shown to be compatible with replicating adenoviruses, when an E1-deleted vector was used in a dual-virus system in conjunction with a replication-competent agent. Here, we constructed a virus that replicates in cancer cells and codes for sCAR-EGF. Interestingly, the oncolytic potency of the novel agent was not improved over nontargeted controls in vitro or in vivo. These results suggest that the expression of biologically active proteins can be counterproductive to virus replication.
Hemminki
Akseli
A
Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, University of Alabama at Birmingham, Alabama 35294-3300, USA. Akseli.Hemminki@Helsinki.Fi
Wang
Minghui
M
Hakkarainen
Tanja
T
Desmond
Renee A
RA
Wahlfors
Jarmo
J
Curiel
David T
DT
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D002460:Cell Line; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004815:Epidermal Growth Factor / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism*; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011991:Receptors, Virus / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000627:therapeutic use*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014779:Virus Replication
C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors