Effect of Repeat Dosing of Engineered Oncolytic Herpes Simplex Virus on Preclinical Models of Rhabdomyosarcoma
Related Experiment Video
Updated: Mar 13, 2026
Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Alicia M Waters1, Laura L Stafman1, Evan F Garner1
1Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, Birmingham, AL, USA 35233.
Abstract:
Rhabdomyosarcoma (RMS), a tumor of skeletal muscle origin, is the most common sarcoma of childhood. Despite multidrug chemotherapy regimens, surgical intervention, and radiation treatment, outcomes remain poor, especially in advanced disease, and novel therapies are needed for the treatment of these aggressive malignancies. Genetically engineered oncolytic viruses, such as herpes simplex virus-1 (HSV), are currently being explored as treatments for pediatric tumors. M002, an oncolytic HSV, has both copies of the γ134.5 gene deleted, enabling replication in tumor cells but thwarting infection of normal, postmitotic cells. We hypothesized that M002 would infect human RMS tumor cells and lead to decreased tumor cell survival in vitro and impede tumor growth in vivo. In the current study, we demonstrated that M002 could infect, replicate in, and decrease cell survival in both embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS) cells. Additionally, M002 reduced xenograft tumor growth and increased animal survival in both ARMS and ERMS. Most importantly, we showed for the first time that repeated dosing of oncolytic virus coupled with low-dose radiation provided improved tumor response in RMS. These findings provide support for the clinical investigation of oncolytic HSV in pediatric RMS.
Insights
Oncolytic herpes simplex virus (HSV) M002 effectively targets and reduces survival of rhabdomyosarcoma (RMS) cells. Combined with low-dose radiation, M002 shows promise for treating pediatric RMS.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Rhabdomyosarcoma (RMS) is a common pediatric skeletal muscle cancer with poor outcomes.
- Novel therapies are urgently needed for aggressive pediatric malignancies like RMS.
- Genetically engineered oncolytic viruses, including herpes simplex virus-1 (HSV), are being investigated for cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of M002, an oncolytic HSV, against human rhabdomyosarcoma cells.
- To determine if M002 can inhibit tumor growth and improve survival in vivo.
- To assess the combined effect of M002 and low-dose radiation on RMS treatment.
Main Methods:
- In vitro studies assessing M002 infection, replication, and cell survival in embryonal (ERMS) and alveolar (ARMS) rhabdomyosarcoma cells.
- In vivo studies using xenograft models to evaluate M002's impact on tumor growth and animal survival.
- Investigation of repeated M002 dosing combined with low-dose radiation therapy.
Main Results:
- M002 successfully infected, replicated in, and reduced cell survival of both ERMS and ARMS cells.
- M002 significantly reduced xenograft tumor growth and increased survival in both ARMS and ERMS models.
- Repeated M002 administration with low-dose radiation demonstrated an enhanced tumor response in RMS.
Conclusions:
- Oncolytic HSV M002 demonstrates significant anti-tumor activity against rhabdomyosarcoma in vitro and in vivo.
- Combination therapy with M002 and low-dose radiation offers a promising strategy for pediatric RMS treatment.
- These findings support further clinical investigation of oncolytic HSV for pediatric RMS patients.
