Fibrosis is a condition lacking therapeutic interventions. The study by Christian Stockmann provides proof of principle for vaccination as an immunotherapeutic approach to treat organ fibrosis (particularly liver and lung).
Proteins encoded by genes specifically expressed in fibrogenic cells result in specific “self-peptides” on the surface on fibrogenic cells and can be turned into immunogenic “antigens” and targets for specific T cell responses upon specific immunization.
n this approach, activation of Adam12 (disintegrin) and Gli1 (transcription factor) genes in profibrotic cells and the resulting autopeptides are exploited to develop T-cell vaccines and eliminate fibrogenic cells.
Therapeutic vaccination against ADAM12 resulted in a decrease in the amount of ADAM12-expressing cells and reduced tissue fibrosis, as evidenced by a significant decrease in activated α-SMA-expressing fibroblasts and tissue collagen content.
Flash Therapeutics’ lentiviral vectors were used for this study - expressing GFP encoding the full-length ADAM12 protein (v-A12, vector construct in Figure S2A) with adjuvants (incomplete Freund's adjuvant (IFA) plus the TLR9 agonist CpG oligodeoxynucleotides (ODN) - and demonstrate their efficacy to mount specific CD8+ T cell responses.
The publication in Cell.com by Michal Sobecki and Christian Stockmann, showing effective in vivo immunotherapy based on vaccination with our lentivirus :