Virotherapy Treatment for Mesothelioma Patients

What is Virotherapy?

Virotherapy is cancer treatment using a virus to find and destroy cancer cells without harming healthy cells.

Types of virotherapy include oncolytic virotherapy, viral immunotherapy and viral vectors, which is also called viral gene therapy.

Viral vectors also can deliver tumor antigens — substances found on cancer cells but not normal cells — into the body. This stimulates an antitumor immune response.

This is similar to how viral immunotherapy works, and sometimes the terms “viral vector therapy” and “viral immunotherapy” are used interchangeably.

While virotherapy is not a cure for mesothelioma, researchers hope that combining it with other therapies will help people live longer with the cancer.

Origins of Virotherapy

More than a century ago, a surgeon named William Coley noticed that cancer patients who developed an infection after surgery sometimes lived longer than patients without infection.

Dr. Coley wondered if the infection triggered the patients’ immune system to attack the cancer. He developed experimental treatments called Coley’s toxins, which some consider one of the first immunotherapy treatments.

Coley’s toxins first used live bacteria injected into tumors and later, heat-killed microbes. The results were unpredictable. Some patients experienced serious infections and died after Coley’s treatments, and the approach fell from favor.

Fortunately, Coley’s early work was not completely forgotten. It laid the foundation for the development of today’s immunotherapy and virotherapy cancer treatments.

How Virotherapy Works

Oncolytic Viruses

Oncolytic viruses infect cancer cells. Some viruses naturally infect cancer cells, while other viruses can be modified in the lab to target specific cancer cell types.

The viruses make their way into cancer cells and reproduce rapidly. The rapid viral reproduction ruptures the membranes of cancer cells and destroys them.

The destroyed cancer cells release antigens, which are substances more easily recognized as foreign by the body. This stimulates the immune system to attack remaining tumors, too.

Oncolytic viruses seem to destroy tumors in two ways: Directly by rupturing cancer cell members and indirectly by stimulating the immune system to better recognize the cancer and attack it.

Researchers are also developing methods to combine gene therapy and virotherapy using oncolytic viruses. One example includes modifying oncolytic viruses to deliver p53 genes, which help the immune system fight cancer.

Viral Immunotherapy

Viral immunotherapy uses a virus to deliver an immune-stimulating substance called an antigen into the body. The antigen helps the immune system recognize and attack cancer cells.

A 2014 phase I clinical trial report published in the medical journal Oncoimmunology describes this type of virotherapy. Researchers evaluated the case of a 68-year-old man with asbestos-related malignant pleural mesothelioma (MPM).

The clinical trial used a type of virus called an adenovirus. The treatment is called ONCOS-102.

When a response is better than expected, the doctors may publish a report detailing these results. In the ONCOS-102 clinical trial, the man survived 18 months from when treatment began and more than 33 months from diagnosis.

The study scientists reported the response as “remarkable,” given the median survival of patients with MPM varies from 4 to 12 months from diagnosis.

Phase I studies test the safety, side effects, best dose and timing of a new treatment. The dose may be increased slowly to find the highest dose that does not cause harmful side effects.

Although phase I clinical trials are not designed to treat or cure patients, the ONCOS-12 clinical trial seemed to treat one participant more effectively than conventional therapy.

Viral Vectors

Viral vectors are created in the lab. Researchers start with a normal virus and alter it to create one that cannot cause disease.

This type of virotherapy is considered a form of gene therapy because the modified viruses alter genes in targeted cells. Targets can include cancer cells or other malfunctioning cells contributing to genetic diseases.

Some viral vectors target malfunctioning mesothelioma genes. One example of this approach uses a virus to disrupt how mesothelioma cells create the proteins that allow uncontrolled cell growth — a hallmark of all cancers.

In another approach, scientists have created a virus targeting mesothelioma genes that make too much of one growth factor. The virus only infects the cells with excessive amounts of the growth-promoting substance.

Viral vectors can kill the cancer cells directly or make them more sensitive to conventional treatments such as chemotherapy and radiation therapy.

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Mesothelioma Virotherapy Clinical Trials

Promising viruses for mesothelioma virotherapy include modified versions of vaccinia, measles, adenovirus, herpes simplex and Newcastle disease virus.

All of these approaches have been studied in clinical trials, though none is approved for widespread clinical use yet. These treatments are only available to mesothelioma patients participating in clinical trials.

A 2021 clinical research study studied the CpHV-1 virus as a potential new mesothelioma virotherapy approach. The researchers found that CpHV-1 strongly synergized with cisplatin, a common chemotherapy medication, and this agent combination did not affect healthy mesothelial cells.

Clinicaltrials.gov currently lists numerous clinical trials using virotherapy approaches. Searching for “mesothelioma and virotherapy” will return results on these trials.

These studies are funded by pharmaceutical companies, cancer centers and government research. For example, the National Cancer Institute has funded some of these studies including a virotherapy mesothelioma clinical trial.

Additionally, certain research centers are conducting virotherapy research for mesothelioma. For example, the National Institutes of Health and Vaccine Immunotherapy Center conduct mesothelioma research on immunotherapy and virotherapy.

Combining Virotherapy and Conventional Cancer Treatment

There are few studies on combinations of virotherapy and chemotherapy. Preclinical (animal) research suggests this approach may be very effective for treating mesothelioma.

One example of preclinical combination therapy research studied mesothelioma virotherapy plus pemetrexed (Alimta) and cisplatin or carboplatin. Pemetrexed and platin chemotherapy drugs are standard of care.

Medical experts accept this standard of care as appropriate treatment for a certain cancer. It is widely used by medical oncology professionals and typically is the first treatment offered when a person is diagnosed with mesothelioma.

This study found that chemotherapy alone did not decrease mesothelioma tumor growth. However, the virotherapy alone slowed tumor growth, and the combination of virotherapy plus chemotherapy delayed tumor growth even more.

The safety and immune-activating properties of this virotherapy in humans is already known. The chemotherapy already is standard of care and widely used to treat mesothelioma.

All of these factors provide a strong rationale for clinical trials testing virotherapy with first-line chemotherapy in patients with malignant mesothelioma. These trials likely will be coming in the near future.