Shajan, Irene;
Rochet, Léa NC;
Tracey, Shannon R;
Jackowska, Bianka;
Benazza, Rania;
Hernandez-Alba, Oscar;
Cianférani, Sarah;
... Albada, Bauke; + view all
(2023)
Rapid Access to Potent Bispecific T Cell Engagers Using Biogenic Tyrosine Click Chemistry.
Bioconjugate Chemistry
10.1021/acs.bioconjchem.3c00357.
(In press).
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Abstract
Bispecific antibodies as T cell engagers designed to display binding capabilities to both tumor-associated antigens and antigens on T cells are considered promising agents in the fight against cancer. Even though chemical strategies to develop such constructs have emerged, a method that readily converts a therapeutically applied antibody into a bispecific construct by a fully non-genetic process is not yet available. Herein, we report the application of a biogenic, tyrosine-based click reaction utilizing chemoenzymatic modifications of native IgG1 antibodies to generate a synthetic bispecific antibody construct that exhibits tumor-killing capability at picomolar concentrations. Control experiments revealed that a covalent linkage of the different components is required for the observed biological activities. In view of the highly potent nature of the constructs and the modular approach that relies on convenient synthetic methods utilizing therapeutically approved biomolecules, our method expedites the production of potent bispecific antibody constructs with tunable cell killing efficacy with significant impact on therapeutic properties.
| Type: | Article |
|---|---|
| Title: | Rapid Access to Potent Bispecific T Cell Engagers Using Biogenic Tyrosine Click Chemistry |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.bioconjchem.3c00357 |
| Publisher version: | https://doi.org/10.1021/acs.bioconjchem.3c00357 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10182370 |
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