A modular platform for Sterically Masked Activated Cytokines (SMACks) - PubMed
3 hours ago
- #targeted therapy
- #cytokine engineering
- #biomedical platform
- A modular platform called Sterically Masked Activated Cytokines (SMACks) was developed for conditionally active cytokines, enabling targeted delivery and reducing pleiotropic effects.
- SMACks are assembled from a targeting Fab/VHH, cytokine, and Fc, with the Fab/VHH providing both masking and targeting functions, as demonstrated with an IL-22 SMACk selective for intestinal epithelial cells.
- Mechanistic analysis revealed that SMACks operate via cis signaling through a reduced on-rate, with tunable format parameters for customization.
- In a mouse colitis model, the IL-22-SMACk showed selective activity in the colon and efficacy, highlighting therapeutic potential.
- The platform's versatility was shown by selectively directing other cytokines like interferon-α, IL-2, IL-4, or IL-7 to CD8+ T cells, indicating broad applicability for cytokine research and therapies.