Combined VSV oncolytic virus and chemotherapy for squamous cell carcinoma.
OBJECTIVE
Vesicular stomatitis virus (VSV) is a negative-strand ribonucleic acid (RNA) virus that replicates specifically in tumor cells and has oncolytic effects in a variety of malignant tumors. We previously demonstrated recombinant VSV vectors incorporating viral fusion protein (rVSV-F) and interleukin 12 (rVSV-IL12) to have significant antitumor effects against squamous cell carcinoma (SCC) in a murine model. Here we evaluate the potential to combine a potent chemotherapeutic agent for SCC (cisplatin) with rVSV-F and rVSV-IL12 to improve efficacy.


METHODS
In vitro, three SCC cell lines were tested using rVSV-F and rVSV-IL12 with cisplatin, monitoring viral replication and cell survival. In an orthotopic floor of mouth murine SCC model, intratumoral injections of virus combined with systemic cisplatin were tested for tumor control and animal survival.


RESULTS
In vitro, virus and cisplatin combination demonstrated rapid replication and enhanced tumor cell kill. Human keratinocytes were unaffected by virus and cisplatin. In vivo, combined rVSV-F with cisplatin reduced tumor burden and improved survival (P = .2 for both), while rVSV-IL12 monotherapy had better tumor control (P = .06) and survival (P = .024) than combination therapy.


CONCLUSIONS
Addition of cisplatin did not affect the ability of either virus to replicate in or kill murine SCC cells in vitro. In vivo, combination therapy enhancedrVSV-F antitumor activity, but diminished rVSV-IL12 antitumor activity. Combination therapy may provide useful treatment for SCC with the development of more efficient viral vectors in combination with different chemotherapy agents or immunostimulatory agents.
Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA.
Chih-Kwang
CK
Sung
Bryan
B
Choi
Georges
G
Wanna
Eric M
EM
Genden
Savio L C
SL
Woo
Edward J
EJ
Shin
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy / Q000821:virology; D018664:Interleukin-12 / Q000235:genetics*; D008562:Membrane Glycoproteins; D051379:Mice; D008809:Mice, Inbred C3H; D009060:Mouth Floor / Q000473:pathology / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D011993:Recombinant Fusion Proteins; D015996:Survival Rate; D018116:Vesiculovirus / Q000235:genetics*; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D018664:Interleukin-12; D002945:Cisplatin