Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats.
Oncolytic virotherapy is a promising strategy for safe and effective treatment of malignancy. We have reported previously that recombinant vesicular stomatitis virus (VSV) vectors are effective oncolytic agents that can be safely administered via the hepatic artery in immunocompetent rats to treat multifocal hepatocellular carcinoma (HCC), resulting in tumor necrosis and prolonged survival. Though the results were encouraging, complete tumor regression was not observed, which led us to explore alternative approaches to further enhance the efficacy of VSV treatment. Transarterial embolization techniques have been shown to improve the efficiency and tumor selectivity of anticancer treatments. Degradable starch microspheres (DSM) are one such embolic agent that provides transient embolization of the therapeautic agent before being degraded by serum amylases. Here we demonstrate via dynamic contrast-enhanced magnetic resonance imaging that in our rat model of multifocal HCC, DSM injection into the hepatic artery results in a substantial reduction in tumor perfusion of systemically applied contrast agent. VSV, when administered in combination with DSM, results in enhanced tumor necrosis and synergistically prolongs survival when compared with VSV or DSM monotherapy.


CONCLUSIONS
This regimen of viroembolization represents an innovative therapeutic modality that can augment the future development of transarterial oncolytic virus therapy for patients with advanced HCC.
Altomonte
Jennifer
J
II. Medical Clinic, Technical University of Munich, Munich, Germany.
Braren
Rickmer
R
Schulz
Stephan
S
Marozin
Sabrina
S
Rummeny
Ernst J
EJ
Schmid
Roland M
RM
Ebert
Oliver
O
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000379:methods*; D006499:Hepatic Artery; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D008297:Male; D008863:Microspheres; D050130:Oncolytic Virotherapy / Q000379:methods*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011915:Rats, Inbred BUF; D013213:Starch; D018116:Vesiculovirus / Q000235:genetics
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013213:Starch