Jha, R;
Kinna, A;
Hotblack, A;
Bughda, R;
Bulek, A;
Gannon, I;
Ilca, T;
... Pule, M; + view all
(2023)
Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein–Protein Interaction.
ACS Chemical Biology
, 19
(2)
pp. 308-324.
10.1021/acschembio.3c00521.
Preview |
Text
jha-et-al-2024-designer-small-molecule-control-system-based-on-minocycline-induced-disruption-of-protein-protein.pdf - Published Version Download (6MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Designer Small-Molecule Control System Based on Minocycline-Induced Disruption of Protein–Protein Interaction |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acschembio.3c00521 |
| Publisher version: | http://dx.doi.org/10.1021/acschembio.3c00521 |
| Language: | English |
| Additional information: | Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0. |
| Keywords: | Minocycline, Tissue Distribution, Cell Communication, Anti-Bacterial Agents, Signal Transduction |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10187883 |
Archive Staff Only
 |
View Item |
