Think of T-cells like an animal protecting their territory. They’re the body’s top defense mechanism, effective at evicting intruders.
However, they’re often ineffective at finding and attacking mesothelioma. Think of an animal with hindered vision, unable to see the damage caused by these highly destructive tumors.
A trial involving both virotherapy and immunotherapy could help these “animals” sniff out mesothelioma cells and prolong the lives of patients.
The Baylor College of Medicine research team has announced Phase II of a clinical trial involving two emerging treatments. Researchers hope combining MTG201, a virotherapy, and the immunotherapy drug nivolumab shows promising results. This phase officially started July 31, according to its ClinicalTrials.gov page, and could last two years.
What Is Pleural Mesothelioma?
There are three types of mesothelioma, a rare cancer which almost always forms in one of three areas of the body. Pleural mesothelioma, the most prevalent type of this disease, originates in the sheet-like membrane separating the chest wall and lung cavity.
Unfortunately, there are few treatments approved by the U.S. Food and Drug Administration for pleural mesothelioma. Patients often are limited to either surgery, chemotherapy, radiation or a combination of those options.
Aside from just a few treatment avenues for patients, the disease is also extremely aggressive and often has a discouraging prognosis.
Dr. Bryan Burt, the lead investigator for the Baylor College of Medicine study, said in a press release on the institution’s website that there has been “minimal” progress in advancing survival for pleural mesothelioma patients.
“The benefit of the current standard treatments for pleural mesothelioma has plateaued,” he added.
Combining treatments — such as surgery and chemotherapy — often yields the best results for mesothelioma patients. Some trials have combined chemotherapy and immunotherapy.
Will immunotherapy paired with virotherapy also prove effective?
Explaining Immunotherapy for Mesothelioma
How can virotherapy and immunotherapy work together to stop mesothelioma? To answer, we must first explain how each works biologically.
Let’s return to the animal analogy from before. PD-1 is a protein that exists on T-cells, the protectors of your body and, ultimately, your health. PD-1 signals for the T-cells to ignore healthy cells and focus on unhealthy ones.
When diseased cells form in the body, the T-cells should locate and attack them like a predator finding an intruder. However, mesothelioma cells use a diversion to escape the T-cells’ focus. They have the PD-L1 protein, which binds with and activates the PD-1. This process tricks the T-cells into ignoring the tumors.
Basically, the T-cells are like a blinded animal.
So how does immunotherapy help? Nivolumab, the generic name for Opdivo, is a popular immunotherapy option for mesothelioma clinical trials. It’s an immune checkpoint inhibitor, one which targets the PD-1 and PD-L1 interaction. By blocking the proteins’ binding together, the immune system’s T-cells identify the mesothelioma cells as dangerous.
Explaining Virotherapy for Mesothelioma
Virotherapy, by comparison, involves reprogramming viruses to help the body. They’ll ignore healthy aspects of the body and focus just on the diseased portion.
MTG201, specifically, is a disabled adenovirus warped to induce cancer cell death. That’s the description given in an article on the Immuno-Oncology News website about the trial. However, the virotherapy has a much longer-lasting effect than just killing one cancer cell.
When the cancerous cells die, they release proteins that elicit an immune system response. Like a shark smelling blood in the water, the T-cells swarm to the location where the disease exists.
And like a shark with new and improved eyesight, the T-cells identify and attack the remaining mesothelioma tumors thanks to the immunotherapy’s effectiveness at blocking the PD-L1.
“This therapy eradicates mouse mesothelioma tumors, rapidly and consistently in an aggressive mouse model of mesothelioma,” Burt said.
Details of the Clinical Trial
The Phase II clinical trial at Baylor involves 12 patients receiving four intratumoral injections of MTG201 across 50 days. Intratumoral means the virotherapy will be administered directly into the cancer location, which is either the pleura or the lung cavity.
The trial participants also will receive intravenous infusions of nivolumab every four weeks. Patients will undergo a computed tomography scan at the four- and 12-week marks, and then every three months afterward. They’ll also undergo biopsies three times, each time just before receiving the MTG201 injection.
Clinical trials for mesothelioma are commonplace, and many are still looking for participants to enroll. If you have mesothelioma, you could be part of a groundbreaking discovery that helps future patients. Additionally, you’ll receive otherwise-unavailable treatment.
For information on joining the Baylor viro-immunotherapy clinical trial or to join another study, contact our patient advocate Jenna Campagna. You can email her at firstname.lastname@example.org to expand your treatment options beyond the FDA-approved list.
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- Clinical trial uses immunotherapy to treat mesothelioma. Baylor College of Medicine. Retrieved from: https://www.bcm.edu/news/cancer/clinical-trial-immunotherapy-mesothelioma. Accessed: 08/13/19.
- MTG201 Plus Nivolumab in Patients With Relapsed Pleural Mesothelioma. U.S. National Library of Medicine. Retrieved from: https://clinicaltrials.gov/ct2/show/study/NCT04013334. Accessed: 08/12/19.
- Upcoming Phase 2 Trial Will Test Opdivo-MTG201 Combo for Malignant Pleural Mesothelioma. Immuno-Oncology News. Retrieved from: https://immuno-oncologynews.com/2019/08/09/upcoming-phase-2-trial-will-test-opdivo-mtg201-combo-refractory-malignant-pleural-mesothelioma/. Accessed: 08/12/19.
- Immune checkpoint inhibitors to treat cancer. American Cancer Society. Retrieved from: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html. Accessed: 07/19/19.
- How Does OPDIVO® Work With My Immune System?. Opdivo. Retrieved from: https://www.opdivo.com/about-opdivo/how-opdivo-works.