Replication competent Semliki Forest virus prolongs survival in experimental lung cancer.
We evaluated the therapeutic potential of the replication competent vector VA7-EGFP, which is based on the avirulent Semliki Forest virus (SFV) strain A7 (74) carrying the EGFP marker gene in an orthotopic lung cancer tumor model in nude mice. We have previously shown that this oncolytic vector destroys tumor cells efficiently in vitro and in vivo (in subcutaneous tumor model). Tumor growth in animals with orthotopically implanted adenocarcinoma cells (A549) were monitored during the study with small animal CT. We show that locally administered virotherapy with VA7-EGFP increased survival rate in experimental lung cancer significantly (p < 0.001) comparable to results obtained with the second generation conditionally replicating adenoviral vector Ad5-Delta24TK-GFP, used for comparison. The limited efficacy in systemically administered oncolytic viruses is the essential problem in oncolytic virotherapy and also in this study we were not able to elicit significant response with systemic administration route. Despite the fact that tumor microenvironment in orthotopic lung cancer is more optimal, viruses failed to home to the tumors and were unable to initiate efficient intratumoral replication. Clearly, the efficacy of virotherapy is influenced by many factors such as the route of virus administration, immunological and physiological barriers and cancer cell-specific features (IFN-responsiveness).
Määttä
Ann-Marie
AM
A. I. Virtanen Institute, Department of Biotechnology and Molecular Medicine, University of Kuopio, Kuopio, Finland. ann-marie.maatta@uku.fi
Mäkinen
Kimmo
K
Ketola
Anna
A
Liimatainen
Timo
T
Yongabi
Felicitas Newu
FN
Vähä-Koskela
Markus
M
Pirinen
Risto
R
Rautsi
Outi
O
Pellinen
Riikka
R
Hinkkanen
Ari
A
Wahlfors
Jarmo
J
D000818:Animals; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral; D005260:Female; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000502:physiology*; D012672:Semliki forest virus / Q000502:physiology*; D014779:Virus Replication