More and more treatment options for cancer patients have been discovered and being optimized by scientists for robust tumor killing outcomes and fewer side effects. Therapies by genetically modifying immune cells, for example, CAR-T cell therapy, and triggering production of tumor specific immune cells by patients themselves have been the hotspot in cancer research.

How does it work?
Since the 19th century, researchers have found that some cancer patients naturally infected with viruses experienced tumor regression, which attracted more and more scientists to decipher the mechanisms behind this magic. It turns out that viruses circulating in patient body enter the tumor microenvironment, infect and kill the tumor cells (oncolytic). Viruses preferentially infect and replicate in tumor cells while more likely to be cleared in healthy cells, which lowers potential side effects. More importantly, lysed tumor cells release large amount of tumor antigens, which provides signals to immune system and activates anti-tumor immunity. In order to activate more powerful tumor killing performance, oncolytic viruses can also be genetically engineered to express signaling molecules for attracting and stimulating anti-tumor immune cells.
What criteria are required for choosing oncolytic virus (OV)?
Many studies focused on exploring possible oncolytic virus candidates for different cancer types. Several factors need to be considered when it comes to choosing proper oncolytic virus: immunogenicity and toxicity of the virus, pre-existing immunity against the virus, barriers in tumor microenvironment, etc..
How are oncolytic viruses injected into cancer patients?
Depending on locations of tumors, administration routes are chosen for the fewest side effects on healthy cell. The most common methods are injecting OV intravenously and intratumorally. Intratumoral administration is optimal due to less contact with surrounding healthy cells compared to IV injections.
What are the remaining concerns about oncolytic virotherapy?
T-VEC, which uses herpesvirus to fight against melanoma and has been approved by FDA. About 40% of patients had complete tumor regression and 20% had partial responses. However, there are still some barriers in oncolytic virotherapy.
In theory, OV do not replicate well in healthy cells and can be cleared from the system, but OV infecting and killing non-tumor cells is still possible, indicating patients who experience the side effects will need to take anti-viral drugs.
When OV is administered intravenously, viral particles might randomly adhere to blood vessels instead of migrating to the tumor sites, so the bioavailability needs to be improved if local injection is not feasible. Recently, some studies have found that certain immune cells can carry OV to the tumor sites since immune cells have their own signaling network, which navigates them to tumor sites.
When OV is immunogenic, the host anti-viral immunity will attack and eliminate the viruses before they enter tumor microenvironment, which drastically impairs its killing efficacy.
More and more studies have shown that oncolytic virotherapy is a promising therapeutic platform for cancer patients, but more optimization is needed for higher efficacy and fewer safety concerns.