Oncolytic Virotherapy Development for Pediatric Cancers (Neuroblastoma)

Neuroblastoma (NB) is one of the most usual extracranial solid tumors in children. It is a classic example of tumors involved in developing tissues, being diagnosed during early childhood. It is derived from neural crest cells, and therefore uniquely expresses the norepinephrine transporter (NET) on its cellular membrane, allowing it a special cancer for the use of targeted therapies and tumor-selective imaging. Oncolytic viruses (OVs) have the promise of killing cancer cells with low toxicities to healthy tissues. OVs infection and selective replication inside tumor cells are based on modifications of the virus genome so as to target specific molecules or signal transduction pathways of cancer. Besides, cell death may also activate antitumor immune responses to further amplify the beneficial effects. Nowadays, there are several results from in vitro and in vivo experiments in which the oncolytic ability of different viruses has been measured in a number of NB cell lines and primary samples. With years of exploration in immunotherapy, Creative Biolabs has established a comprehensive OncoVirapy™ platform. We are capable of developing specific oncolytic virotherapy strategy for neuroblastoma, as well as providing OVs construction and validation services to customers all over the world.

Oncolytic Virotherapy for Neuroblastoma

Usually, the treatment of recurrent neuroblastoma is based on where the tumor recurred, the previous treatment, tumor biology and the possible gene mutations. Common treatment strategies for NB include chemotherapy, targeted delivery of radionuclides, retinoids, angiogenesis inhibitors, tyrosine kinase inhibitors, as well as aurora kinase inhibitors. The application of virotherapy against NB is an emerging field. There are a number of OVs having been attempted to treat NB, such as Adenoviruses, Herpesviruses, Newcastle Disease Virus, Parvovirus, Poliovirus, as well as Seneca Valley Virus. Take the FusOn-H2 as an example, it is a type 2 HSV which selectively targets tumor cells with an activated Ras signaling pathway. FusOn-H2 eliminates tumor cells via a direct cytolytic effect and through syncytia formation and apoptosis. It not only kills NB cells but also leads to an essential anti-NB immune response which has been exhibited in the Neuro-2a model by intratumoral injection.

Fig 1. Diversity of oncolytic viruses and their modes of action. (Ungerechts, G., 2016)

Combination Therapy

Despite treating NB as a monotherapy, OVs are also enable to be used as combination therapy with targeted radiation therapies. For example, a recent study showed that oHSV has been used to deliver the NET transgene to tumor cells to increase susceptibility to ¹³¹I-MIBG. MIBG (meta-iodobenzylguanidine) is a form of targeted radiation therapy for high-risk neuroblastoma when bound to 131Iodine. In this study, they evaluated the efficacy of HSV1716/NET in improving NET expression and hence enhancing the efficacy of ¹³¹I-MIBG. The final date showed that neuroblastoma cell lines are susceptible to HSV1716/NET, and upon viral infection, an effective transfer of the NET gene will lead to an improvement in ¹³¹I-MIBG uptake.

Based on our advanced OncoVirapy™ platform, Creative Biolabs are confident in providing novel OVs and developing more efficient oncolytic virotherapy strategies for our customers. Please contact us for more information and a detailed quote.

References:

1. Ramirez, M., (2010). "Oncolytic virotherapy for neuroblastoma." Discovery medicine, 10(54), 387-393.
2. Ungerechts, G., (2016). "Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses." Molecular Therapy-Methods & Clinical Development, 3, 16018.

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