Rapid access to potent bispecific T cell engagers using biogenic tyrosine click chemistry

Irene Shajan, Léa N. C. Rochet, Shannon R. Tracey, Bianka Jackowska, Rania Benazza, Oscar Hernandez-Alba, Sarah Cianférani, Christopher J. Scott, Floris L. van Delft, Vijay Chudasama*, Bauke Albada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
35 Downloads (Pure)

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.
Original languageEnglish
JournalBioconjugate Chemistry
Early online date14 Nov 2023
DOIs
Publication statusEarly online date - 14 Nov 2023

Keywords

  • Organic Chemistry
  • Pharmaceutical Science
  • Pharmacology
  • Biomedical Engineering
  • Bioengineering
  • Biotechnology

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