Oncolytic vaccinia virotherapy of anaplastic thyroid cancer in vivo.
BACKGROUND
Anaplastic thyroid carcinoma (ATC) is a fatal disease with a median survival of only 6 months. Novel therapies are needed to improve dismal outcomes.


OBJECTIVE
A mutated, replication-competent, vaccinia virus (GLV-1h68) has oncolytic effects on human ATC cell lines in vitro. We assessed the utility of GLV-1h68 in treating anaplastic thyroid cancer in vivo.


METHODS
Athymic nude mice with xenograft flank tumors of human ATCs (8505C and DRO90-1) were treated with a single intratumoral injection of GLV-1h68 at low dose (5x10(5) plaque-forming unit), high dose (5x10(6) plaque-forming unit), or PBS. Virus-mediated marker gene expression (luciferase, green fluorescent protein, and beta-galactosidase), viral biodistribution, and flank tumor volumes were measured.


RESULTS
Luciferase expression was detected 2 d after injection. Continuous viral replication within tumors was reflected by increasing luciferase activity to d 9. At d 10, tumor viral recovery was increased more than 50-fold as compared with the injected dose, and minimal virus was recovered from the lung, liver, brain, heart, spleen, and kidneys. High-dose virus directly injected into normal tissues was undetectable at d 10. The mean volume of control 8505C tumors increased 50.8-fold by d 45, in contrast to 10.5-fold (low dose) and 2.1-fold (high dose; P=0.028) increases for treated tumors. DRO90-1 tumors also showed significant growth inhibition by high-dose virus. No virus-related toxicity was observed throughout the study.


CONCLUSIONS
GLV-1h68 efficiently infects, expresses transgenes within, and inhibits the growth of ATC in vivo. These promising findings support future clinical trials for patients with ATC.
Lin
Shu-Fu
SF
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Price
Daniel L
DL
Chen
Chun-Hao
CH
Brader
Peter
P
Li
Sen
S
Gonzalez
Lorena
L
Zhang
Qian
Q
Yu
Yong A
YA
Chen
Nanhai
N
Szalay
Aladar A
AA
Fong
Yuman
Y
Wong
Richard J
RJ
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000473:pathology; D014183:Transplantation, Heterologous; D014616:Vaccinia virus / Q000276:immunology*; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000627:therapeutic use*
D019496:Cancer Vaccines; D005819:Genetic Markers; D014765:Viral Vaccines