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 themajority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered oneof the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, andnew therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapyfor 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 thyroidcarcinoma were also established to evaluate the in vivo anti-tumor efficacy of G47Δ. Materials and
Methods:The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with G47Δ at differentmultiplicities 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 G47Δ or mock. Tumor volumes and mouse survival times were documented.
Results: G47Δwas 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 modestsensitivity to G47Δ, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplasticthyroid carcinoma cell lines (ARO and FRO) were highly sensitive to G47Δ; G47Δ significantly inhibited tumorgrowth and prolonged the survival of mice bearing s.c. ARO and FRO tumors.
Conclusions: The oHSV G47Δcan effectively kill different types of human thyroid carcinomas in vitro. G47Δ significantly inhibited growth ofanaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, G47Δ may hold great promisefor thyroid cancer patients.