TS-000873 — The current timeframe required for current Good Manufacturing Product (cGMP) validation and approval is significant. The delay between development and approval is time intensive and the advancements that can improve treatment can be outdated by the time they reach the market. Genetic modifications would lead to restarting the production and approval process and delaying the introduction of the entry into human trials. Dr. Kevin Cassady and his team found that combinations of oncolytic viruses (OV) can be combined using current, approved cGMP stocks can be employed effectively and subsequently saving time that would have been spent on re-engineering, production, and validation, as well as the expense associated. The clinical outcome would be improved as this new process allows for a more rapid and cost-effective approach to clinical translation using existing stock of virus.

TS-000854 — Dr. Kevin Cassady and his team have identified an amino acid epitope encoded from Syndecan 4 (SDC4) that binds to a receptor protein on immunosuppressive myeloid and dendric cells called GPNMB. This group has developed a series of fusion proteins including FcGamma (Fcγ) fusions to encode the binding GPNMB-interacting domain, and shared antigens containing epitope tags. They have incorporated the fusion into virus expressed antigens to target myeloid cells in the tumor microenvironment in order to change their functional activity and enhance uptake and processing of antigens. Because SDC4 and GPNMB act as co-inhibitory molecules, they anticipate that fusion proteins will disrupt this interaction, which will enhance T cell activity and could be used as an anti-cancer immunotherapy.

TS-000842 — In gene expression studies from early oHSV clinical trials, it was found that the cytokine IL27 is a potential target for therapeutic optimization. The cytokine’s expression levels are observed to be directly related to the improvement of the patient survival following treatment that includes an oncolytic HSV. Early data collected by Dr. Kevin Cassady confirms that the virus-based expression correlates with improved survival, and reduced tumor cell growth and has cleared immune cells from the tumors as well.

TS-000738 — In all living cells, extracellular vesicles (EVs) are naturally produced. Drs. Kevin Cassady and Uksha Saini have developed a streamlined approach to utilize these EVs to deliver biologics and clinical drug treatments that permit repeated treatments without the possibility of limiting therapeutic delivery due to the natural immune response. This method produces an immune inert drug delivery system that, unless the EVs are designed to encode immunostimulatory molecules, should not invoke an immune response. Our preliminary studies show that we can load extracellular vesicles (EVs) with a therapeutic payload of our choice. Retroviruses co­opt and use much of the same pathways involved in cellular EV production for virus exit of the infected cell. We therefore hypothesized that Lentiviruses (a non-replicating retrovirus commonly used in the lab for gene expression) would provide a modifiable platform to generate therapeutic gene products that that would be preferentially transported and packaged into cellular EVs. This platform could then be modified and developed as a potential therapeutic delivery platform.

TS-000556 — Oncolytic viruses (OVs) target cancer cells, killing them from the inside. As the contaminated cancer cells die, the biproducts develop additional infectious components that continue to destroy the tumor. Dr. Kevin Cassady and his team have found that using OV-based “shared” antigen expression allows the immune system to recognize these antigens and improves the capacity of the immune system to fight tumor activity. Shared antigen expression includes proteins that are overexpressed by many tumors. They have been able to construct additional OVs that improve the immune targeting glioma and its associated antigen, IL13Ra2. This group is simultaneously investigating other ways enhance the anti-glioma activity by combining OVs with Chimeric Antigen Receptor-targeted T cells directed against IL13Ra2. In pre-clinical trials, this combination has produced improved anti-tumor activity with lower doses and safe to the patient.

TS-000387 — Oncolytic viruses infect and replicate in tumor cells without harming normal tissue. Researchers at Nationwide Children’s Hospital have genetically engineered sophisticated ‘Herpes Simplex Viruses’ (HSVs) that express tumor associated antigens. These HSVs have elicited superior antitumor immune response against tumors in preclinical mouse models. These next generation HSVs are a valuable therapeutic option for controlling cancers.