Treatment of anaplastic thyroid carcinoma in vitro with a mutant vaccinia virus.

Overview

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a fatal disease resistant to all conventional treatments. Novel therapies are needed to improve dismal outcomes. METHODS: A replication-competent vaccinia virus (GLV-1h68) was engineered by inserting expression cassettes encoding Renilla luciferase-green fluorescent protein (GFP), beta-galactosidase, and beta-glucuronidase into the genome of LIVP strain. Infection of 6 ATC cell lines by GLV-1h68 was detected in vitro at 12, 24, and 36 hours. Viral proliferation was measured through viral plaque assays. Cytotoxicity was measured daily at a multiplicity of infection (MOI) of 0.01, 0.1 and 1. RESULTS: Viral infection was detected in all cell lines by 24 hours and increased in intensity at 36 hours. Logarithmic viral replication was detected in all cell lines. At MOI 1, <13% cell survival was measured in 5 cell lines by day 7. At MOI 0.01, 3 cell lines showed <21% cell survival by day 7. Luciferase and beta-galactosidase activity at 24 hours correlated with cytotoxicity at MOI 0.01 on day 5. CONCLUSION: A replication-competent vaccinia virus has significant infectious and oncolytic activity against a panel of human ATC. These results encourage future in vivo and clinical studies for this novel agent to treat this fatal cancer.