Treatment of human thyroid carcinoma cells with the g47delta oncolytic herpes simplex virus.
BACKGROUND
Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, G47Δ, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of G47Δ.


METHODS
The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with G47Δat different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either G47Δor mock. Tumor volumes and mouse survival times were documented.


RESULTS
G47Δ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to G47Δ, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to G47Δ G47Δ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors.


CONCLUSIONS
The oHSV G47Δ can effectively kill different types of human thyroid carcinomas in vitro. G47Δ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, G47Δ may hold great promise for thyroid cancer patients.
Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China E-mail : liur@vip.163.com.
Jia-Ni
JN
Wang
Li-Hua
LH
Xu
Wei-Gen
WG
Zeng
Pan
P
Hu
Samuel D
SD
Rabkin
Ren-Rin
RR
Liu
D000818:Animals; D049109:Cell Proliferation; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D018139:Simplexvirus / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D023041:Xenograft Model Antitumor Assays