WHAT IS ONCOLYTIC VIROTHERAPY?
Oncolytic Virotherapy is an exciting, increasingly recognized discipline in cancer research. Although the connection between viruses and cancer regression was recognized in the early 20th century, it wasn’t until the recent development of advanced genetic engineering techniques that true progress has been made using virotherapy to attack and destroy cancer cells. Today, researchers can modify existing viruses to create new oncolytic viruses that are less susceptible to immune suppression while more specifically targeting particular classes of cancer cells. Additionally, these modified oncolytic viruses can be adapted to insert and express cancer-suppressing genes and diagnostic proteins.
In the last few years, preclinical and clinical trials evaluating a range of novel genetically engineered oncolytic viruses have reported very encouraging results. Among those drawing interest and demonstrating intriguing results:
- > Intra-tumoral delivery of Herpes Simplex Virus (HSV) in Melanoma and Head and Neck cancer
- > Reovirus delivered in combination with chemotherapy in a variety of cancers
- > Intra-tumorally or intravenously delivered Vaccinia Viruses (VV) in a wide range of solid tumor cancers
- > Countless preclinical studies involving these and other viruses, possibilities for combination therapeutic approaches, etc.
Indeed, the body of scientific and medical evidence surrounding oncolytic viruses is converging on one important point: Oncolytic Virotherapy is emerging as a viable, targeted new treatment modality for cancer patients. For the first time, these novel strategies hold great promise to make a significant impact in both outcomes and quality of their lives.
Oncolytic viruses refer to those viruses that are able to eliminate malignancies by direct targeting and lysis (killing) of cancer cells within the tumor, leaving non-cancerous cells unharmed. Oncolytic viruses by definition have a natural attraction to cancer cells (tropism), though their safety profile in patients, selectivity and replication competence vary significantly by type and strain of virus. Among the oncolytic viruses being studied in preclinical and clinical trials are Adenovirus, Herpes Simplex Virus, Vesticular Stomatic Virus, Reovirus, Coxsackie virus and Vaccinia Virus.
Importantly, some oncolytic viruses have recently been shown to be capable of destroying cells that are typically resistant to conventional chemotherapy and/or radiation. Many also have synergistic effects when administered in combination with these conventional therapies. Select viruses can even carry therapeutic and/or diagnostic payloads directly inside tumors. And, with the first approval in 2005 of the oncolytic adenovirus H101 for human use in China, more sophisticated, safe and effective oncolytic viral therapies will inevitably be approved for the benefit of cancer patients, either as monotherapies, or for use in combination with currently marketed drugs and conventional therapies.
The ultimate challenge in the field of oncolytic virotherapy is to produce an “ideal” oncolytic therapy that is:
Highly selective – able preferentially to seek and enter tumor cells while sparing non-cancerous tissues and cells
Replication competent: – maximally-efficient in making copies of itself, amplifying in and destroying tumor cells
Well-tolerated – having minimal side effects in cancer patients, and even more importantly,
non-pathogenic; in human patients
Carries little to no risk of genomic integration – viruses that do not integrate into the host cell DNA (replicate only in the cytoplasm) do not carry this risk, and therefore no risk of mutation
Systemically administered – in metastatic disease, the most clinically relevant approach is to target and eliminate cancer cells, tumors and metastases wherever they are located in the body.
Able to carry therapeutic or diagnostic payloads directly to the tumor – specific strains of oncolytic virus can be engineered to insert and express cancer-suppressing genes and/or anti-cancer therapies
Genelux believes vaccinia is the best-suited oncolytic virus for human cancer therapy and for this reason has developed a broadly applicable, attenuated (Lister strain) vaccinia virus-based platform technology for its novel oncolytic cancer therapies and diagnostics.