Immunotoxin clinical trials are testing a type of immunotherapy in mesothelioma patients. It uses immune-modulating drugs to selectively target and kill cancer cells. The trials with mesothelioma patients show promise and may include combinations with other treatments.
What Is an Immunotoxin?
Immunotoxins are targeted compounds that use designed molecules to attach to cancer cells. As a targeted treatment, the goal of the medication is to seek out the specific cancer cells and deliver a toxic payload directly into the cancer while leaving normal cells relatively unharmed.
An immunotoxin is a combination of a designed antibody and a toxin. The antibody is designed to find and attach to proteins called antigens on the surface of cancer cells. The cell then absorbs the toxin and dies.
While toxins have long been used to treat cancer through chemotherapy, that treatment is generally not specific. Chemotherapy drugs circulate the entire body, killing cancer cells and healthy cells.
The immunotoxin strategy specifically targets and kills cancer cells, which should reduce the side effects while increasing the amount of the drug that can reach the cancer.
Can Immunotoxins Treat Mesothelioma?
Many of the immunotoxins under development target a biomarker called mesothelin. Mesothelioma cells usually produce this marker, so it is a good target for immunotoxin therapy.
Several clinical trials have finished, are ongoing, or are being planned to determine if immunotoxins can treat mesothelioma. Results have been mixed so far, but show the most success when immunotoxins are combined with other treatments.
Animal studies with immunotoxins have also provided interesting results. A recent study used a mouse model to determine if an immunotoxin called LMB-100 could produce anti-tumor immunity.
The mice with mesothelioma received treatment with LMB-100. Those treated successfully were reintroduced to tumor cells to see if they had developed immunity.
The immunotoxin did affect the immune system, giving researchers more information about how immunotoxin drugs change the tumor environment. It could be useful going forward with similar treatments for human mesothelioma patients.[1]
Completed Immunotoxin Mesothelioma Clinical Trials
Researchers have been studying immunotoxins in many cancer types for years. Some are using these therapies to target mesothelioma cancer cells.
SS1P Immunotoxin
A clinical trial that began in 2011 showed promise for patients with mesothelioma. This phase I trial used an immunotoxin known as SS1P, which combines an anti-mesothelin targeting antibody with a toxin derived from a type of bacteria called Pseudomonas.[2]
In one trial with SS1P, 60% of patients had stable disease when the drug was combined with other drugs. One patient had a stunning response, with a 74% reduction in tumor size. In this trial, the drugs combined SS1P with immunosuppressants.[2]
Results were even more positive than those seen with the chemotherapy drugs. In previous trials, patients’ immune systems recognized and began developing antibodies that destroyed the immunotoxin treatment used to target the cancer cells.
Combining the treatment with immunosuppressant drugs reduced this activity, and the immunotoxin worked more effectively.[2]
LMB-100 Immunotoxin
A phase I study of LMB-100 reported results in 2020 and has since moved into additional trials. This early trial determined that, when used alone, LMB-100 had limited effectiveness in mesothelioma patients.[3]
The trial was useful in determining dosing and any adverse events that might threaten patients. Ongoing studies with LMB-100 are combining it with chemotherapy and other immunotherapy drugs.
Terminated Immunotoxin Clinical Trials
While trials with immunotoxin drugs for mesothelioma have produced some promising results, others have had unexpected results. None are currently active, and some have been terminated for low enrollment or adverse events.
Mesothelin-Targeted Immunotoxin LMB-100 in Combination With SEL-110 in Subjects With Malignant Pleural or Peritoneal Mesothelioma
A phase I trial tested the combination of an immunotoxin known as LMB-100 with an immunosuppressant called SEL-110. Both pleural and peritoneal mesothelioma patients participated in the trial.[4]
Although this combined therapy has great potential for treating mesothelioma, researchers stopped recruitment due to adverse reactions.
Several patients developed a severe type of pneumonitis, an inflammation of the tissue around the lungs. Pneumonitis can cause difficulty breathing, coughing, fatigue, and loss of appetite. While recruitment for this trial was stopped, no results for effectiveness in the original participants have been reported.[4]
Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma
This study recruited patients with pleural or peritoneal mesothelioma who did not have good results with standard first-line treatments or could not undergo surgery.
Researchers administered LMB-100, an immunotoxin, by injecting it directly into tumors. Patients also received the immunotherapy drug ipilimumab. Unfortunately, the trial was terminated early due to low enrollment numbers.[5]
Potential Adverse Events of Immunotoxin Treatment
Immunotoxin therapy is still very new, so all potential side effects are not yet known. One potential risk is hepatotoxicity or liver damage. Liver function may decline in patients receiving immunotoxin therapy.
Other recorded side effects include vascular leak syndrome (which causes swelling and edema), pleuritic syndrome (inflammation of the pleural tissue), and hemolytic uremic syndrome (which can cause anemia and kidney damage).[2]
How Can Mesothelioma Patients Access Immunotoxin Therapy?
Because this is still an experimental type of treatment, clinical trials are the best way for patients to benefit from it. Talk to your medical team to determine if you are eligible for the two trials recruiting or planning to recruit mesothelioma patients.
Immunotoxin therapy is an emerging approach to cancer treatment that is being tested for a wide variety of cancers. There is great hope for patients with difficult-to-treat cancers like mesothelioma. These clinical trials may someday show that combinations of immunotoxins with other drugs could extend patient lives. If you are interested in trying these therapies, talk to your medical team about finding and enrolling in an appropriate immunotoxin clinical trial.
