Branched oncolytic peptides for the treatment of cold tumors

The present tetrabranched dendrimer peptides, with a cationic and amphipathic chemical structure, have demonstrated significant in vitro effectiveness as inducers of immunogenic cell death, with high selectivity against cancer cells.

The branched structure confers stability in serum for over sixteen hours. In vitro tests on pancreatic cancer cell lines (PANC-1 and Mia PaCa-2) confirmed the peptides' ability to bind specifically and dose-dependently, compared to non-cancerous cell lines (immortalised murine macrophages).

The peptides also demonstrated specific cytotoxic activity against human pancreatic adenocarcinoma cell lines (PANC-1), while maintaining a non-toxic profile in CHO-K1 cells even at concentrations one hundred times higher.

The release of immunogenic cell death markers (e.g., HMGB1) following the specific cytotoxicity of the peptides has also been confirmed in PANC-1 cells, similar to the well-known chemotherapeutics daunorubicin and irinotecan.

Conversely, the peptides can stimulate IFN-β secretion and ATP release more effectively and for a longer duration than daunorubicin or irinotecan.