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.

Fig. 1 Type of Sarcoma

Clinical Studies of OVs

JX-594, a replication-competent strain of vaccinia virus, has been engineered with the Franulocyte–Macrophage Colony-Stimulating Factor (GM-CSF). It has displayed evidence of anti-tumor effects in a variety of refractory tumors, such as melanoma, hepatocarcinoma, and lung cancers. A Phase I clinical trial shows that JX-594 selectively infects, replicates, and expresses transgene products in advanced, treatment-refractory metastatic solid tumors comprising one sarcoma after intravenous infusion while sparing normal tissues.

Another case is NTX-010, a replication competent Seneca Valley virus. NTX-010 synthesizes the dsRNA stimulated PKR that usually results in inhibiting protein synthesis. Nevertheless, the majority of tumors have dysregulated PKR signaling. There is a selective proliferation of the RNA virus. When it was determined against the in vitro panel of tumors of the Pediatric Preclinical Testing program, it exhibited significant responses in 9 out of the 23 cell lines tested at the highest concentration. The tumors that are most sensitive to NTX-010 are rhabdomyosarcoma, neuroblastoma, rhabdoid tumor, as well as 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.

References:

1. Lettieri, C. K., (2012). “Progress of oncolytic viruses in sarcomas.” Expert review of anticancer therapy, 12(2), 229-242.
2. Galanis, E. (2011). “Cancer: Tumour-fighting virus homes in.” Nature, 477(7362), 40-41.

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