• BMB Reports
• /
• v.36 no.4
• /
• pp.379-386
• /
• 2003

A mutant herpes simplex virus 1, mtHSV, was constructed by inserting the E. coli beta-galactosidase gene into the loci of icp34.5, the apoptosis-inhibiting gene of HSV. The mtHSV replicated in and lysed U251 (human glioma cells), EJ (human bladder cells), and S-180 (mice sarcoma cells), but not Wish (human amnion cells) cells. With its intact tk (thymidine kinase) gene, mtHSV exhibited susceptibility to acyclovir (ACV), which provided an approach to control viral replication. An in vivo test with mtHSV was conducted in immune-competent mice bearing sarcoma S-180 tumors, which were treated with a single intratumoral injection of mtHSV or PBS. Tumor dimensions then were measured at serial time points, and the tumor volumes were calculated. Sarcoma growth was significantly inhibited with prolonged time and reduced tumor volume. There was microscopic evidence of necrosis of tumors in treated mice, whereas no damage was found in other organs. Immunohistochemical staining revealed that virus replication was exclusively confined to the treated tumor cells. HSV-1 DNA was detected in tumors, but not in the other organs by a polymerase chain reaction analysis. From these experiments, we concluded that mtHSV should be a safe and promising oncolytic agent for cancer treatment.

• Korean Journal of Head & Neck Oncology
• /
• v.22 no.2
• /
• pp.130-136
• /
• 2006

Introduction : The sensitivity of tumor cells to radiotherapy is a critical determinant of local control and potential cure in advanced head and neck squamous cell carcinoma(HNSCC). The emergence of radioresistant tumor cells is an obstacle to cancer therapy. Most radioresistant cells have a higher proportion of cells in the Sphase of the cell cycle and a lower apoptotic fraction than radiosensitive cells. HSV replication is increased in cells that have higher S-phase fractions. NV1066 is an oncolytic herpes simplex virus type-1 mutant. We hypothesized that NV1066 replication and cytotoxicity are increased in radioresistant cells. The purpose of this study is to evaluate the antitumor efficacy of NV1066 to treat radioresistant HNSCC. Methods : Radioresistant cells were selected by treating five HNSCC cell lines with repeated conventional fractionated doses of radiation(2Gy/day), using a Cs-137 irradiator, up to a cumulative dose of 70Gy. Clonogenic cell survival and S-phase fractions were compared between radioresistant and parental radiosensitive cells. The two cell populations were then treated with NV1066 to examine viral replication, by the viral plaque assay and viral cytotoxicity. Results : Fractionated irradiation resulted in the selection of radioresistant cells. Radioresistant cells had a higher S-phase fraction(42.9%) compared to parental cells(26.2%). NV1066 replication in radioresistant cells was 7.4 times higher than in parental cells(p<0.01). Treatment with NV1066 resulted in increased cytotoxicity of 24.5% in radioresistant cells compared to parental cells(p<0.05). Conclusion : NV1066 showed increased viral replication and cytotoxicity in radioresistant HNSCC cell lines. These findings suggest a potential clinical application for this oncolytic viral therapy as treatment for radioresistant head and neck cancers.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1241-1245
• /
• 2015

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, $G47{\Delta}$, 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 $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at 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 $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ 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 $G47{\Delta}$, 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 $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.