CKS1-derived oncolytic peptide NF27 clears murine tumors with low toxicity
- A series of peptides derived from CKS1 was designed to define what governs oncolytic activity, focusing on a proline-induced hinge and how hydrophilic and hydrophobic residues are arranged in space.
- The lead, NF27, killed a broad range of cancer cells while sparing healthy cells and causing little red blood cell lysis.
- Cell size and cell-cell junctions emerged as correlates of how sensitive a cell type is to these peptides.
- In mice, NF27 triggered immunogenic cell death, drew immune cells into tumors and slowed growth, with complete regression in some animals and no systemic toxicity seen.
💡 Points
For a membrane-lytic peptide, selectivity comes down to physical properties rather than a binding mode, so the cell-size and junction correlations count for more than any potency readout. If sensitivity follows tissue architecture, the therapeutic window will likely shift between tumor types and models. I would track hemolysis and serum stability for every analog and pin down whether the hinge or the amphipathic layout drives the SAR.