Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein-Protein Interaction.

ABSTRACT: A versatile, safe, and effective small-molecule control system is highly desirable for clinical cell therapy applications. Therefore, we developed a two-component small-molecule control system based on the disruption of protein-protein interactions using minocycline, an FDA-approved antibiotic with wide availability, excellent biodistribution, and low toxicity. The system comprises an anti-minocycline single-domain antibody (sdAb) and a minocycline-displaceable cyclic peptide. Here, we show how this versatile system can be applied to OFF-switch split CAR systems (MinoCAR) and universal CAR adaptors (MinoUniCAR) with reversible, transient, and dose-dependent suppression; to a tunable T cell activation module based on MyD88/CD40 signaling; to a controllable cellular payload secretion system

SUBMITTER: Jha R 

PROVIDER: S-EPMC10877577 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature