Immunotoxin clinical trials are testing a type of immunotherapy that uses immune-modulating drugs to target and kill cancer cells selectively. 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.
Clinical Trials Using SS1P Immunotoxin
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.
Supported by the National Cancer Institute, 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.
Immunotoxin Trial Recruitment Halted
While trials have produced some promising results with immunotoxin drugs for mesothelioma, others have had unexpected results.
A phase I trial tested the combination of 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.
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.
- 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.
Potential Adverse Events
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).
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 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.