Written By: Devin Golden
Mesothelioma Virotherapy
Mesothelioma virotherapy uses viruses to recognize and attack cancerous mesothelial cells, breaking them apart and inspiring an immune response. Another form of virotherapy uses viruses as vectors for gene therapy. Mesothelioma virotherapy is emerging through clinical trials and research.
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Important Facts About Mesothelioma Virotherapy
- Virotherapy is a treatment for mesothelioma that uses manipulated forms of viruses to attack mesothelioma cells while leaving healthy cells alone.
- There are different forms of virotherapy. The most common is oncolytic viruses, which infect cancer cells and kill them from within.
- ONCOS-102, a type of oncolytic virus with an immune-stimulating effect, is the closest to FDA approval for mesothelioma. The therapy’s survival rates are close to two years.
How Does Virotherapy Work as a Cancer Treatment?
Years of research proves viruses can attack cancer. Doctors are learning how to harness these infectious agents for fighting deadly diseases.
Viruses are a small collection of code with a protein “coat.” They infect the body’s healthy cells and use those cells as a “host,” replicating themselves within the host cell. During the replication process, the virus breaks up and kills the host cell. The virus then moves to other cells to continue replicating.
Researchers create viruses in laboratories and alter their genetics, usually to ignore healthy cells and focus on mutated, cancerous cells. These viruses can enter cancer cells, replicating like above and breaking up the diseased cells. This is how virotherapy shrinks a cancerous tumor or prevents it from growing any further.
Using Virotherapy for Mesothelioma
Mesothelioma is a cancer of the mesothelium, which is a set of thin, protective linings in the body. These linings are made up of mesothelial cells. When these mesothelial cells mutate malignant mesothelioma forms.
The mesothelial linings include the:
- Pleura, a lining around both lungs
- Peritoneum, a lining around the abdominal cavity
- Pericardium, a lining around the heart
This cancer quickly evolves past the host lining and towards the nearby organs. It also spreads as multiple microscopic tumors rather than one large ever-growing mass.
Virotherapy attacks diseased mesothelial cells just as it would other cancer cells. It infiltrates the cells and breaks them up, stopping them from spreading.
To summarize how virotherapy for mesothelioma works:
Doctors create a modified virus
The virus enters the cancer area within the body and infects the cells or delivers another therapy to fight the disease
The virus replicates and breaks up the mesothelioma cells from the inside
The virotherapy ignores healthy cells due to the modifications and may die after its anti-tumor response
Types of Mesothelioma Virotherapy
Virotherapy has multiple applications for treating and stopping cancer. There are three main types of virotherapy:
- Oncolytic viruses
- Viral vectors for other therapies
- Viral immunotherapy
Oncolytic Viruses
These viruses directly attack mesothelioma cells. They enter the cells and use them as hosts. The viruses then break the cells apart, killing them and slowly shrinking the size of a tumor.
Oncolytic viruses are programmed to:
- Not replicate once they infect cells
- Ignore healthy cells
In some cases, doctors create the programs to die once it breaks apart the host mesothelioma cell.
Oncolytic viruses also can help the immune system. The broken-apart mesothelioma cells release antigens. These antigens can serve as blueprints for the immune system to locate mesothelioma cells with similar antigens.
An example of an oncolytic virus with an immune-stimulating aspect is ONCOS-102 for mesothelioma. This therapy received FDA fast-track designation early in 2021.
Other examples are:
- GL-ONC1, a modified form of the vaccinia virus that stopped smallpox, which is part of a clinical trial at Memorial Sloan-Kettering Cancer Center
- MV-NIS, a form of the measles virus, and part of a clinical study at the Mayo Clinic
- Tiny gold nanotubes that enter the cell, absorb light, and cause the cells from overheating
Viral Vectors for Other Therapies
Virotherapy can serve as a transport for other therapies, most notably gene therapy or immunotherapy. The viruses act as a cargo train and immediately shut down once they reach the destination, which is the site of mesothelioma.
Viral Immunotherapy
Viral immunotherapy uses the virus’ presence in the body to stimulate an immune response. The immune system’s T-cells are charged with seeking and killing unwanted intruders, ranging from common cold viruses to deadly cancerous tumors.
By inserting a virus into the disease location, the T-cells respond in droves to the site. This puts them in the vicinity of the mesothelioma cells. The viruses usually cause an event that allows the T-cells to properly recognize mesothelioma cells as dangerous to the body.
ONCOS-102 and Interferon Alpha-2B are both examples of viral immunotherapy.
Benefits of Virotherapy for Mesothelioma
Virotherapy is a fast-rising treatment method for numerous reasons. Most notably, it can improve survival time as a second-line option after other therapies failed.
The benefits of virotherapy are based on the current standard of treatment for mesothelioma. Surgery is the first option, but most patients aren’t candidates due to their age, health and the cancer’s spread.
Chemotherapy is the next option as a maintenance therapy. For virotherapy to emerge as a new standard option for mesothelioma, it must outperform chemotherapy both in survival and safety.
Improved Survival Time
Virotherapy has outperformed chemotherapy in a few clinical trials, most notably ONCOS-102. The median survival rate for ONCOS-102 with chemotherapy is 22-25 months at the two-year follow-up. The survival rate for chemotherapy on its own is 14 months.
TR002, the viral vector therapy delivering a gene therapy, performed well in a phase 2 trial:
Fewer Side Effects
Virotherapy causes fewer side effects than chemotherapy. This is a significant benefit to the treatment.
Chemotherapy often causes severe nausea, fatigue and weight loss. Virotherapy side effects depend on the type of virus used, along with the target location for the therapy.
Virotherapy can cause flu-like symptoms, such as chills, fatigue, nausea and fever. These might be the immune system responding to the virus’ presence, although the virus is programmed to ignore healthy cells. Therefore, the effects should be mild.
Option for Late-Stage Patients
Late-stage mesothelioma patients have few therapeutic options. Most researchers look for a treatment to permanently stall the disease’s growth. This would turn mesothelioma into a manageable chronic illness.
Ongoing Research and Studies Involving Mesothelioma Virotherapy
Quite a lot of ongoing studies feature virotherapy for mesothelioma. ONCOS-102 is the most noteworthy one, with an upcoming trial to combine the oncolytic virus with a checkpoint inhibitor immunotherapy drug.
If you’re interested in virotherapy trials, please contact our medical staff. We can help you find a study close to your residence, making participation easier.
Common Questions About Virotherapy for Mesothelioma
How does virotherapy work for mesothelioma?
Virotherapy inserts viruses into the tumor site to disrupt cancer cells from growing. The virotherapy drug either attacks tumors or escalates the immune system’s ability to fight cancer by activating the T-cells and other cancer-fighting mechanisms to recognize mesothelioma tumors.
What are the types of virotherapy?
There are three main types of virotherapy used for mesothelioma where a virus is used as a vector to put a therapeutic agent into the body:
- Oncolytic virus, which directly kills cancer cells.
- Virotherapy with gene therapy, which transfers a gene therapy drug into the tumor site and reprograms cancer cells to die.
- Viral immunotherapy, which stimulates the immune system by putting an unwanted virus in the body.
Does virotherapy improve survival for mesothelioma patients?
Virotherapy is featured in quite a few clinical trials, but more research is needed before declaring any objective survival benefit for mesothelioma patients. ONCOS-102, for instance, is an oncolytic adenovirus that activates the immune system. In the latest study, requiring further investigation, ONCOS-102 plus chemotherapy improved mesothelioma survival by six months.
Sources & Author
- Intrapleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma. Clinicaltrials.gov. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT01766739. Accessed: 03/24/2021.
- Efficacy & Safety of rAd-IFN Administered With Celecoxib & Gemcitabine in Patients With Malignant Pleural Mesothelioma. U.S. National Library of Medicine. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03710876. Accessed: 10/02/19.
- Tiny golden bullets could help tackle asbestos-related cancers. EurekAlert. Retrieved from: https://www.eurekalert.org/pub_releases/2020-10/uoc-tgb102620.php. Accessed: 10/29/2020.
- ONCOS – Oncolyctic Virus. Targovax. Retrieved from: https://www.targovax.com/en/oncos-oncolyctic-virus/. Accessed: 01/28/2020.
- Continued survival benefit in Targovax’s ONCOS-102 trial in mesothelioma at the 21-month follow-up. PRNewswire. Retrieved from: https://www.prnewswire.com/news-releases/continued-survival-benefit-in-targovaxs-oncos-102-trial-in-mesothelioma-at-the-21-month-follow-up-301233073.html. Accessed: 02/23/2021.
- Oncolytic Virus Therapy. Cancer Research Institute. Retrieved from: https://www.cancerresearch.org/immunotherapy/treatment-types/oncolytic-virus-therapy. Accessed: 03/24/2021.
- Trizell Ltd. announces Phase 3 pivotal study of interferon alfa-2b gene therapy in malignant pleural mesothelioma. PRNewswire. Retrieved from: https://www.prnewswire.com/news-releases/trizell-ltd-announces-phase-3-pivotal-study-of-interferon-alfa-2b-gene-therapy-in-malignant-pleural-mesothelioma-300815572.html. Accessed: 03/25/2021.
