Oncolytic Virotherapy Development for Sarcomas
Nowadays, oncolytic virotherapy has emerged as a promising treatment of many types of solid tumors. Sarcomas, malignant tumors of mesenchymal origin, derived from cells that would commonly mature into skeletal muscle, smooth muscle, fat, fibrous tissue, nerve, bone, vascular tissue, and cartilage, which are typically categorized into bone sarcomas and soft tissue sarcomas. Recently, Oncolytic Viruses (OVs) have been applied to the treatment of this challenging cancer, receiving inspiring results. Several progresses have been made in genetic engineering of the viruses, such as increasing the capacity of the virus to infect tumor cells, operating the virus with transgenes which promote the virus' ability to kill tumor cells, as well as engineering the virus to improve concomitantly administered therapies. With years of exploration in immunotherapy, Creative Biolabs has established a comprehensive OncoVirapy™ platform. We are capable of developing specific oncolytic virotherapy strategy for sarcomas, as well as providing OVs construction and validation services to customers all over the world.
Oncolytic Viruses for the Treatment of Sarcomas
Despite some progress has been made in the increased overall survival of pediatric patients with common sarcomas on account of advances in multiagent chemotherapy, however, little success has been obtained in the treatment of metastatic and relapsed disease. The strategies of sarcoma treatment have been expanding to comprise new agents, for example, immune modulators, IGF-1 receptor antibodies, mTOR inhibitors, and other biologic agents in an effort to promote survival for these patients. Research of OVs for the treatment of pediatric sarcomas has improved over the past decade with many types of OVs studied for the treatment of sarcomas, including Adenovirus, Herpes virus, Vaccinia, Reovirus, Seneca Valley virus, Newcastle disease virus, Semliki Forest, as well as Vesicular stomatitis viruses. At present, there remain six clinical trials exploring the treatment of resistant sarcomas with OVs.
Clinical Studies of OVs
A replication-competent strain of vaccinia virus, engineered with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), has shown evidence of anti-tumor effects in various refractory tumors, including melanoma, hepatocarcinoma, and lung cancers. A Phase I clinical trial demonstrates that this modified virus selectively infects, replicates, and expresses transgene products in advanced, treatment-refractory metastatic solid tumors, including one sarcoma, after intravenous infusion, while sparing normal tissues.
Another case involves a replication-competent Seneca Valley virus, which synthesizes dsRNA that stimulates PKR, typically leading to the inhibition of protein synthesis. However, most tumors exhibit dysregulated PKR signaling, allowing for the selective proliferation of the RNA virus. When tested against an in vitro panel of tumors in the Pediatric Preclinical Testing program, the virus demonstrated significant responses in 9 out of 23 cell lines tested at the highest concentration. The tumors most sensitive to this virus include rhabdomyosarcoma, neuroblastoma, rhabdoid tumor, and glioblastoma.
The field of oncolytics is approaching the complex balance of controlling the innate antiviral immune response with the potential for an adaptive antitumor immune attack. Based on our advanced OncoVirapy™ platform, Creative Biolabs is confident in providing novel OVs for sarcomas therapy and developing more efficient oncolytic virotherapy strategies for our customers.