A research team led by the University of Zurich (UZH) has developed a vaccination-based immunotherapy to target fibroblasts of the cells in the lung and liver in mice. Their findings may lead to a potentially effective treatment for fibrosis.

The findings are published in the journal Cell Stem Cell in an article entitled, “Vaccination-based immunotherapy to target profibrotic cells in liver and lung.”

“Fibrosis is the final path of nearly every form of chronic disease, regardless of the pathogenesis,” wrote the researchers. “Upon chronic injury, activated, fibrogenic fibroblasts deposit excess extracellular matrix, and severe tissue fibrosis can occur in virtually any organ. However, antifibrotic therapies that target fibrogenic cells, while sparing homeostatic fibroblasts in healthy tissues, are limited. We tested whether specific immunization against endogenous proteins, strongly expressed in fibrogenic cells but highly restricted in quiescent fibroblasts, can elicit an antigen-specific cytotoxic T-cell response to ameliorate organ fibrosis.”

“In animals, we were able to trigger an immune response similar to that to a vaccination, in which the activated connective tissue cells were destroyed while the resting fibroblasts were left unharmed,” explained study leader Christian Stockmann, professor, at the Institute of Anatomy at the UZH.

The researchers studied the differences between the surfaces of resting and of activated connective tissue cells. “Our computer-assisted analyses revealed that fragments of two surface proteins—Adam12 and Gli1—which can be detected by the immune system, are present in large numbers on activated fibroblasts, while there are very few on the resting cells,” explained Stockmann.

The researchers then used these two surface structures as a vaccine in mice in order to trigger an immune response via cytotoxic T cells.

“With the newly developed immunotherapy, we were able to eliminate fibroblasts efficiently in mice, thus reducing fibrosis in the liver and the lungs, without affecting healthy organ tissue,” said Stockmann.

Further studies are needed, but these findings pave a path for vaccine-based immunotherapy for humans in the future.

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