The relationship between viruses and cancers has always been contentious. The idea that viruses may play a role in the pathology of specific cancers traces back to the 19th century. However, the connections aren’t always negative. Oncolytic viruses can also target and lyse tumor cells, acting as a sophisticated anti-cancer therapy. Since the discovery of these special viruses, clinicians have attempted to harness their power to fight cancer. To date, these efforts have shown limited success and modest clinical benefit, in part due to the patient's own immune system responding and destroying the oncolytic viruses before they can effectively target and kill cancer cells.
Newer approaches to oncolytic viral deployment are designed to address this obstacle. Here, we explore how these advanced therapeutic systems enable oncolytic viruses to reach their full potential.
Surviving the immune system
Using oncolytic viruses in cancer treatment is not a novel idea. According to a 2022 review published in the American Journal of Translational Research, as of October 1, 2021, 408 clinical trials have been conducted for 31 oncolytic virus-based products, where 80 percent of the trials were Phase 1 and Phase 2 studies. Most oncolytic viruses are strategically engineered in the lab to increase their tumor-suppressive and immune-modulatory effects. Unfortunately, many of these treatments have stalled because of the documented ability of patients’ immune systems to quickly eliminate these therapeutic agents. This persistent roadblock has prevented oncolytic viruses from progressing into real-world clinical applications.
Innovative solutions to getting oncolytic viruses into the clinic
A new approach has emerged to overcome this specific challenge. It involves packaging oncolytic viruses into allogeneic (donor) stem cells to bypass the rigorous defense of patients’ immune systems. These stem cells act as tiny Trojan horses, shielding the oncolytic viruses from immunological destruction. Importantly, the oncolytic viruses are able to replicate inside the stem cells, significantly enhancing the therapeutic potential of this approach.
In a matter of days, the viruses are released from the stem cells and attack both the injected tumors and distal tumor sites through the treatment-induced immune cells. This approach circumvents immunological destruction of the oncolytic viruses, activates the immune system to target cancer cells, and instantly modifies the tumor microenvironment, creating a one-two punch of cancer-defeating treatment.
This technology could usher in a new era in oncolytic virus-based therapeutics. Using stem cells as a viral delivery system reduces costs, protects the virus, and improves the safety profile of these therapeutics.
These innovations have already begun to prove their worth. One application of this technology has advanced through a Phase 1 clinical trial for the treatment of advanced solid tumors and has shown early signs of both potent anti-cancer effects and safety. Another program has completed a Phase 1 clinical trial for the treatment of glioblastoma and is preparing to launch a Phase 2 trial shortly. If successful, the applications are broad. Oncolytic viruses can be used across many cancer types. Future trials may focus on cancers with significant unmet medical needs, including brain tumors, advanced unresectable melanoma, triple-negative breast cancer, and head and neck cancers.
By packaging oncolytic viruses inside of stem cells, the relationship between viruses and cancers is set to be transformed once again.