Liver fibrosis might be treatable with selective immunotoxins

Chronic alcohol abuse and hepatitis can injure the liver and lead to fibrosis, the buildup of collagen and scar tissue. As a potential approach to treating liver fibrosis, University of California San Diego School of Medicine researchers and their collaborators are looking for ways to stop liver cells from producing collagen.

So we thought…what if we take immunotoxins and try to get them to kill collagen-producing cells in the liver. If these antibodies carrying toxic molecules can find and bind the cells, the cells will eat up the 'gift' and die."

Tatiana Kisseleva, MD, PhD, Team Lead, Associate Professor of Surgery, UC San Diego School of Medicine

In a study published July 12, 2021 in Proceedings of the National Academy of Sciences, Kisseleva and collaborators provide the first evidence that liver fibrosis might be treatable with immunotoxins designed to bind a protein called mesothelin. Mesothelin is rarely found in the healthy human body. Only cancer cells and collagen-producing liver cells, known as portal fibroblasts, make the protein.

Kisseleva teamed up with co-author Ira Pastan, MD, at the National Cancer Institute, part of the National Institutes of Health (NIH). Pastan is co-discoverer of mesothelin and an expert on using immunotoxins to target the protein on cancer cells. He leads several clinical trials testing the approach to treat patients with ovarian cancer, mesothelioma and pancreatic cancer.

To test Pastan's immunotoxins in the context of liver fibrosis, Kisseleva's team first needed a model. Since the immunotoxins specifically recognize human mesothelin, a traditional mouse model of liver fibrosis wouldn't work. Instead, they transplanted human liver cells isolated from patients to mice and treated them with the anti-mesothelin immunotoxin.

Compared to untreated mice, 60 to 100 percent of human mesothelin-producing cells were killed by the immunotoxins, which also reduced collagen deposition.

Treatment for liver fibrosis is currently very limited. According to the NIH, weight loss is currently the only known method for reducing liver fibrosis associated with non-alcoholic fatty liver disease. Alcoholic liver disease is most commonly treated with corticosteroids, but they are not highly effective. Early liver transplantation is the only proven cure, but it is offered only at select medical centers to a limited number of patients.

"What we want to know now is, can this same strategy be applied to other organs?" Kisseleva said. "Surprisingly enough, the same cells are responsible for fibrosis in the lung and kidneys. This is especially exciting because we already know from Dr. Pasten's cancer clinical trials that anti-mesothelin immunotoxins are safe in humans, potentially speeding up their application in other areas."

Source:
Journal reference:

Nishio, T., et al. (2021) Immunotherapy-based targeting of MSLN+ activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis. PNAS. doi.org/10.1073/pnas.2101270118.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoLifeSciences.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
From Bone Regeneration to Heart Repair: Stem Cell Transplantation Paves the Way for New Medical Frontiers