Monotherapy with oncolytic viruses
Current research on viruses indicates that malignant cell death can be caused by nearly every virus and in almost all types of tumours. The first of these studies was conducted at the end of the 1940s by Alice Moore who was the first scientist to prove that viruses had innate oncolytic properties. She did so by prescribing them to patients with a variety of different malignant tumours. In recent years, the range of studied viruses has expanded significantly. The objective in most of these studies was to determine the safety of a given virus and to discover its efficacy and its effect on overall life expectancy. Only somewhat recently were studies conducted where immunity indicators were analysed, a course of research that was studied in Latvia as far back as the 1970s and 1980s.
So far, oncolytic viral monotherapy has had mixed results. It’s possible that this can be explained by the patient’s resistance to the virus and its prompt elimination. It’s also possible that, given the heterogeneousness of tumours, resistance can be created after a period of time. To combat this, a number of different methods with varying mechanisms of action are often used in oncology. It’s been observed that the synergistic combination of oncolytic viruses with other drugs actually increase the potency of the treatment and this method of therapy is even more effective than monotherapy.
Oncolytic virotherapy in combination with other methods
In accordance with the proclamations of the 2016 ESMO (European Society for Medical Oncology) Congress, virotherapy is one of the most promising fields of study in oncology that will produce a flood of new treatments to fight cancer in the future. During the congress, the enormous potential of bacterial (remember William Coley’s toxin!) and viral oncology treatments were mentioned time and again. The goal isn’t to create one universal virus to treat all cancers, but rather to develop a specific oncolytic virotherapy for specific tumours. By combining chemotherapy with oncolytic viruses, the potential cancer cell destroying effect can be increased. A large dose of chemotherapy can destroy the majority of cancer cells and a virus would have no place to gain a foothold. Therefore, the combination of a virus with a low dose of chemotherapy is currently being studied with guarded enthusiasm. It’s believed that the virus can be much more effective when chemotherapy has already taken a bite of the majority of cancer cells.
Chemotherapy drugs in combination with oncolytic viruses not only increase the potency of the cytotoxic effect, but can also remove any hurdles preventing the oncolytic virus from being successful. A variety of reovirus combinations with chemotherapy drugs have been studied in certain in vitro prostate cancer cell lines. Alternatively, by combining a reovirus with docetaxel in vivo, the size of tumours have been reduced and life expectancy increased. This was also confirmed by phase I and II clinical trials using a reovirus in combination with carboplatin and paclitaxel in patients with advanced tumours and a separate group with head and neck area metastatic tumours. This combination was not only well-tolerated, but also indicated a conclusive increase in life expectancy.
Checkpoint inhibitors have been successfully used in a variety of tumour treatments, including those used for melanomas. There have also been new reports that oncolytic viruses regulate the expression of PD-1 / PD-L1 inhibitors on the surface of cancer cells, so it would therefore be wise to combine these agents. A recently published study showed promising results when the T-VEC drug was combined with anti-CTLA-4 antibodies, which is being followed by a phase III trial adding T-VEC to anti-PD-1 antibodies. Other studies have also begun using a combination of CAVATAK, a non-genetically modified coxsackievirus, with a variety of checkpoint receptor inhibitors.
Some oncolytic viruses are known to affect angiogenesis, which improves the vascular permeability of tumours. Therefore, prescribing angiogenesis inhibitors may negatively affect the success of the oncolytic virus. Finally, the modulation of the body’s immune response with chemotherapy drugs can be at odds with the therapeutic effect of the oncolytic virus. Since chemotherapy drugs still play a significant role in the treatment of tumours, it’s only logical that attempts be made to combine them with a variety of different viruses.
In recent years, the number of studies and published articles on the combination of oncolytic viruses with other immunotherapy methods, and even radiation, has only increased. It seems that the role of viruses in the future will only gain in significance.