Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein-Protein Interaction.
ACS Chem Biol
; 19(2): 308-324, 2024 02 16.
Article
in En
| MEDLINE
| ID: mdl-38243811
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 based on IL12 KDEL retention; and as a cell/cell inducible junction. This work represents an important step forward in the development of a remote-controlled system to precisely control the timing, intensity, and safety of therapeutic interventions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Communication
/
Minocycline
Language:
En
Journal:
ACS Chem Biol
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos