Cytotoxic effects of the oncolytic herpes simplex virus HSV1716 alone and in combination with cisplatin in head and neck squamous cell carcinoma.
CONCLUSIONS
HSV1716 alone and combined with cisplatin was efficacious in destroying head and neck squamous cell carcinoma (HNSCC) cells. Combination treatment with HSV1716 and cisplatin gave additive efficacy. These results indicate that HSV1716 in combination with cisplatin could be of therapeutic value in HNSCC and warrants further investigation.


OBJECTIVE
HSV1716 is a replication competent herpes simplex virus which selectively replicates and lyses actively dividing cells but not normal or terminally differentiated cells. The objective of this study was to determine the efficacy of HSV1716 alone and in combination with cisplatin in HNSCC.


METHODS
Three HNSCC cell lines were studied; UM-SCC 14C, UM-SCC 22A and UM-SCC 22B. The permissivity of HSV1716 in these cell lines was determined using multicycle growth experiments. In vitro, cytotoxicity of HSV1716 and cisplatin was determined using an MTS proliferation assay. Isobologram analysis was used to determine the interaction between HSV1716 and cisplatin combination treatment.


RESULTS
The three HNSCC cell lines studied were permissive for HSV1716 replication. Cytotoxicity increased in a dose-dependent fashion in all three cell lines. Cisplatin was non-toxic to the virus. Isobologram analysis showed additive cytotoxicity when HSV1716 was combined with cisplatin in all three cell lines.
Mace
A T M
AT
Department of Otolaryngology, Glasgow University, Glasgow, UK. alastairmace@btinternet.com
Harrow
S J
SJ
Ganly
I
I
Brown
S M
SM
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D006224:Cricetinae; D004359:Drug Therapy, Combination; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D018139:Simplexvirus / Q000502:physiology*; D016896:Treatment Outcome; D014779:Virus Replication
D000970:Antineoplastic Agents; D002945:Cisplatin