New and innovative opportunity for cancer patients
Oncolytic virotherapy is an emerging treatment modality which uses replication-competent viruses to destroy cancer. Oncolytic viruses selectively infect and damage cancerous tissues without causing harm to normal tissues. Many, if not most, naturally occurring viruses have a preferential, although non-exclusive, tropism for tumors and tumor cells.
Inducing death of cancer cells
Oncolytic viruses can kill infected cancer cells in many ways, ranging from direct virus-mediated cytotoxicity through a variety of cytotoxic immune effector mechanisms. Following viral replication, oncolytic viruses induce cell death, which can directly eliminate viable tumor cells, but also set the stage for initiating systemic immune responses.
Mobilizing the immune system to fight cancer
Cancer cells have evolved sophisticated strategies for avoiding immune-mediated destruction. Tumor cells and the microenvironment can express immune-inhibitory surface receptors that inactivate effector immune cells and secrete factors that facilitate the recruitment of immune-suppressive cells, such as tumor-associated macrophages and myeloid-derived suppressor cells, to sites of tumor growth. Oncolytic viruses modify this suppressive micro-environment. These changes promote immune-mediated tumor cell recognition and eradication. Thus, virotherapy mobilizes the natural defenses of the immune system against foreign genetic information that has entered the body and at the same time also against genetically modified cells and tissues, including malignant cells.
Virotherapy alone or in combination for the good of the patient
Some oncolytic viruses have recently been shown to be capable of destroying cells that are typically resistant to conventional chemotherapy and/or radiation. Therefore, oncolytic virotherapy is of special importance for chemotherapy-resistant tumors, like melanoma. Oncolytic viruses could be used both as monotherapy and in complex with other therapies. Besides, compared to cytotoxic and radiation therapy, tumor cell break-down products are eliminated much faster after virotherapy.
The principal target of oncolytic viruses is similar to that of radiotherapy and chemotherapy – a cancer cell.
Benefits of oncolytic virotherapy
Oncolytic virotherapy differs from conventional and even targeted treatments in several essential advantages:
- it is highly selective and able preferentially seek and enter tumor cells while sparing non-cancerous tissues and cells;
- so far, no resistance has been evaluated during oncolytic virotherapy;
- it stimulates the natural defense system of the body by activating immunity, which other treatment methods usually suppress;
- it is maximally efficient in replicating inside cancer cells and destroying tumor tissue;
- it is well tolerated having minimal side-effects in cancer patients, and even more importantly – oncolytic viruses are non-pathogenic in humans;
- it carries little to no risk of genomic integration as viruses do not integrate into the host cell DNA (replicates only in cytoplasm) and therefore no risk of mutation;
- it can be applied for tumors that are not sensitive to radiotherapy and chemotherapy like melanoma;
- it can be used in various treatment phases: before or after the surgery or in between radiotherapy or chemotherapy sessions;
- it could be administered both locally (directly into the tumor tissue or closely around it) and systematically.
It takes time for virotherapy to demonstrate it’s the effect
It may take a longer period of time for oncolytic virotherapy to start expressing its activity. Thus, the conventional response assessing criteria may differ from those for conventional chemotherapy as it works quicker. Sometimes a pseudo-progression may be observed in the very beginning of treatment due to infiltration of tumor tissue with lymphocytes. Therefore the response should be checked after another time period.