Selective antibodies that contain toxins can help treat liver fibrosis

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

“So we thought … and if we take immunotoxins and try to kill the collagen-producing cells in the liver? “said team leader Tatiana Kisseleva, MD, PhD, associate professor of surgery at UC San Diego School of Medicine.” If these antibodies that carry toxic molecules can find and bind the cells, the cells will eat the “gift” and die. “

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

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

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

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

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

“What we want to know now is that this same strategy can be applied to other bodies?” “Kisseleva said.” “Surprisingly, the cells themselves are responsible for fibrosis in the lungs and kidneys. This is especially exciting because we already know about Dr. Pasten’s cancer. clinical trials that anti-mesothelin immunotoxins are safe in humans, which may accelerate their application in other areas. ”