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 an antigen 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 introduced again to tumor cells to see if they had developed immunity.
The immunotoxin did affect the animal 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.
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.
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 bacteria called Pseudomonas aeruginosa.
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 immune suppressants.
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 immune-suppressant drugs, reduced this activity and the immunotoxin worked more effectively.
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.
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.
Active and Terminated Immunotoxin Clinical Trials
While trials have produced some promising results with immunotoxin drugs for mesothelioma, others have had unexpected results. Others are still active, no longer recruiting participants, and awaiting results.
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 immune suppressant called SEL-110. Both pleural and peritoneal mesothelioma patients participated in the trial.
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 original participants have been reported.
Mesothelin-Targeted Immunotoxin LMB-100 in Combination With Tofacitinib in Persons With Previously Treated Pancreatic Adenocarcinoma, Cholangiocarcinoma and Other Mesothelin Expressing Solid Tumors
This study is combining LMB-100 with another immunotherapy drug. It includes people with bile-duct cancer, pancreatic cancer, and other solid tumors that express mesothelin, including mesothelioma.
Clinical Trials Currently Recruiting Mesothelioma Patients
- Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma. In this trial, researchers need hope to determine the safe dose of LMB-100 combined with an immunotherapy drug.
- Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin. This study is not yet recruiting patients, but will need pleural mesothelioma patients. They will undergo cytoreductive surgery followed by perfusion in the chest cavity. Before closing the surgical incision, the surgeons will wash the chest cavity with LMB-100 for 90 minutes. The researchers plan to follow up with participants for two years.
Potential Adverse Events of Immunotoxin Treatment
Immunotoxin therapy is still very new; therefore, 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).
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.Get Your FREE Mesothelioma Packet
Page Written by Mary Ellen Ellis
Mary Ellen Ellis has been the head writer for Mesothelioma.net since 2016. With hundreds of mesothelioma and asbestos articles to her credit, she is one of the most experienced writers on these topics. Her degrees and background in science and education help her explain complicated medical topics for a wider audience. Mary Ellen takes pride in providing her readers with the critical information they need following a diagnosis of an asbestos-related illness.
Page Medically Reviewed and Edited by Kyle J. Becker, PharmD, MBA, BCOP
Kyle J. Becker, PharmD is certified by the Board of Pharmacy Specialties in Oncology Pharmacy. Dr. Becker earned his pharmacy degree from Shenandoah University and he currently serves as an oncology pharmacist at Parkview Cancer Institute.