Exploring the Use of Weakened Viruses for Cancer Treatment

Scientists at Northwestern Medicine have found that an attenuated virus can aid in the elimination of cancer in mice. Furthermore, mice given this virus treatment had a higher lifetime tumor-prevention rate.

Even in immunosuppressed mice, the attenuated virus known as lymphocytic choriomeningitis virus (LCMV) remains safe and effective. This is a crucial discovery because many cancer patients with suppressed immune systems are receiving chemotherapy and other cancer treatments.

An important aspect about this viral-based therapy is that it demonstrates safety and efficacy even in an immunosuppressed host. Mice that were devoid of their killer T cells and their B cells were nonetheless responsive to this therapy.”

Pablo Penaloza-MacMaster, Study Corresponding Author and Assistant Professor, Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

The Northwestern researchers demonstrated that injecting this virus into tumor-bearing mice reduced the tumor and improved survival in several tumor models, including melanoma and colon cancer.

The study was published in The Journal of Clinical Investigation.

LCMV induces a high immune response, but it can cause disease especially, in transplant patients. With molecular biology, however, it is possible to weaken this virus and render it attenuated for use as a safe therapy, while still being immunogenic. The other advantage is that it seems that the same LCMV therapy can be used for various types of cancer.”

Pablo Penaloza-MacMaster, Study Corresponding Author and Assistant Professor, Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

Currently, so-called "oncolytic viruses," such as herpes, are used to treat some types of cancer due to their ability to kill cancer cells. Yet, Penaloza-MacMaster noted that these treatments are ineffective against some tumors and that using them raises safety issues, particularly in immunosuppressed patients. This highlights the need for safer substitutes.

The therapy did more than just help remove the tumors; it also helped shield these mice from developing cancer in the future. Tumor development was less likely to occur in healthy mice that received the LCMV therapy early in life.

The phenomenon under investigation may be accounted for by “trained immunity,” a poorly understood biological process. An earlier infection can lead to a condition known as “trained immunity,” which improves the immune system's capacity to fight off infections in the future. For instance, research indicates that children immunized against tuberculosis (TB) also show enhanced protection against other microorganisms. This is not like the usual vaccination response, like the SARS-CoV-2 vaccine, which mainly guards against this particular virus.

Essentially, this therapy might be providing broader immune protection, helping the body to guard against different diseases beyond the original target.”

Pablo Penaloza-MacMaster, Study Corresponding Author and Assistant Professor, Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

In cooperation with Dr. Seth Pollack, the Director of the Sarcoma Program at Lurie Cancer Center , and Steven T. Rosen, Professor of Cancer Biology at Feinberg, the next phase of this research will test the strategy on canines with sarcoma. If the dogs exhibit improvement as well, researchers intend to begin a human clinical trial utilizing the therapy.

How Does a Virus Treat Cancer?

Tumors are adept at avoiding the immune system’s reaction by devising plans to keep the immune system away from the tumor. The act of injecting the virus into the tumor causes it to exhibit indicators, similar to red flags, alerting the immune system to the presence of an intruder.

Key immune cells like T cells, B cells, and macrophages were absent from the immunosuppressed mice. The virus was still able to fight the cancer by activating other immune pathways in spite of the absence of these vital immune cells. Interferons, which are chemicals that alert the body to an invader and assist in mobilizing the defense systems, are one way it accomplished this.