What Is Virotherapy?

Virotherapy is an emerging treatment option for mesothelioma and other forms of cancer. Currently, clinical studies are gathering information about virotherapy to target mesothelioma. Virotherapy, or oncolytic virotherapy, has been used to treat cancer for the last 40 years.

Evidence of viruses working to destroy cancer tumors dates back to the early 1900s. Bone surgeon and cancer researcher William Bradley Coley compared x-ray images of cancer patients who developed an infection after surgery and noticed some patients lived longer than uninfected patients. Coley later went on to study immune responses and set the stage for modern immunotherapy treatment.

The oncolytic virus contains unique mechanisms that can continually infect and destroy cancer cells. Commonly known oncolytic viruses include human reovirus, parvoviruses H-1, minute virus of mice, vesicular stomatitis virus, and the Newcastle disease virus. 

Oncolytic viruses used as therapeutic agents in the treatment of cancer include human reovirus, myxoma virus, parvovirus H-1, human adenoviruses, Newcastle disease virus, testicular stomatitis virus, bovine herpesvirus 4, and coxsackievirus. Advances in molecular biology and virology have given researchers the tools to study the development of genetically engineered viruses.

Virotherapy for Cancer Treatment

Virotherapy treatment for cancer works by infecting cancer cells. As the cancer cells reproduce quickly, the virus spreads and destroys them. The destroyed cells then cause the tumors to shrink. Many viruses occur naturally, but non-natural viruses are engineered in a lab using biotechnology. The viruses can destroy tumors through immune system stimulation or by rupturing cancer cell membranes. 

There are three branches of virotherapy which are:

  • Anti-cancer oncolytic viruses
  • Viral vectors for gene therapy
  • Viral immunotherapy

Each branch involves different types of treatment methods, including gene overexpression, gene knockout, and suicide gene delivery.

As we know, oncolytic virotherapy uses viruses to destroy cancer cells by infecting them. Viral immunotherapy, however, uses the virus to stimulate the immune system to destroy the cells. The third branch, viral vectors, are modified in the lab to target and alter cancer cell genes.

Virotherapy treatment can be combined with chemotherapy and radiation therapy to extend the lives of cancer patients. Recent studies involving a variety of leukemias and solid tumors indicated promising anti-cancer results. The approach has been used with standard therapies to treat various cancers, including:

  • Mammary carcinoma
  • Hepatocellular carcinoma
  • Colon adenocarcinoma
  • Glioma
  • Prostate cancer
  • Cervical carcinoma
  • Cervical cancer
  • Liver cancer
  • Thyroid cancer
  • Laryngeal cancer
  • Rhabdomyosarcoma

Side Effects of Virotherapy

Patients who have used virotherapy have shown a few side effects in clinical settings. Patients may experience some minor side effects of virotherapy, including flu-like symptoms such as fever, chills, nausea, and muscle aches. The most significant side effect may include an inflammatory response to the treatment. Overall, the therapy has been tolerable among most patients.

Some standard treatments cause severe side effects due to a weakened immune system. Virotherapy, however, only targets cancerous cells and spares non-cancerous ones. The selectivity of cells makes oncolytic viruses produce few side effects.

Virotherapy Treatment in Clinical Trials

Researchers are hoping to combine virotherapy with standard mesothelioma treatments to shrink tumors and hopefully help patients live longer. Virotherapy treatment for mesothelioma includes several promising viruses, including modified versions of measles, herpes simplex, Newcastle disease virus, vaccina, and adenovirus. Mesothelioma patients who participate in clinical trials have access to virotherapy treatment. The emerging treatment is not yet available for widespread use.

A Phase I clinical trial recently completed in early 2021 investigated the side effects of intrapleural measles virus therapy in treating pleural mesothelioma patients. Researchers anticipated that the virus would locate, infect, and kill cancer cells. Additionally, the researchers expected the virus to trigger an immune response that would destroy the remaining cancer cells. We anticipate researchers will post the results shortly.

Previously, Mesothelioma Hub spoke with Dr. Daniel H. Sterman, Director of the Multidisciplinary Pulmonary Oncology Program at New York University’s Langone Health, about a Phase 3 clinical trial involving virotherapy. 

Malignant pleural mesothelioma patients who tried and failed first-line chemotherapy treatment were eligible to receive a genetically-modified adenovirus to deliver new DNA to their cells. Researchers, including Dr. Sterman, engineered the virus to deliver the specific genes to the cancer cells. Patients received the alpha-2b gene directly to mesothelioma tumors present in the body. Patients received other medications and a chemotherapy drug, called gemcitabine.

The Phase 2 study results of adenovirus for mesothelioma treatment indicated the survival time increased around 17 months after receiving the viruses, gemcitabine, and Celebrex (anti-inflammatory medication).

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