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Programmable multispecific DNA-origami-based T-cell engagers
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Programmable multispecific DNA-origami-based T-cell engagers
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Journal Article
Programmable multispecific DNA-origami-based T-cell engagers
2023
Overview
Multispecific antibodies have emerged as versatile therapeutic agents, and therefore, approaches to optimize and streamline their design and assembly are needed. Here we report on the modular and programmable assembly of IgG antibodies, F(ab) and scFv fragments on DNA origami nanocarriers. We screened 105 distinct quadruplet antibody variants in vitro for the ability to activate T cells in the presence of target cells. T-cell engagers were identified, which in vitro showed the specific and efficient T-cell-mediated lysis of five distinct target cell lines. We used these T-cell engagers to target and lyse tumour cells in vivo in a xenograft mouse tumour model. Our approach enables the rapid generation, screening and testing of bi- and multispecific antibodies to facilitate preclinical pharmaceutical development from in vitro discovery to in vivo proof of concept.
A synthetic nanocarrier based on DNA origami chassis offers control over valency, orientation and spatial arrangement of antibodies for simultaneously engaging immune signalling pathways, checkpoint inhibition and targeted co-stimulation in anticancer immunotherapy in vivo.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Assembly
/ Chemistry and Materials Science
/ DNA
/ Humans
/ Lysis
/ Mice
/ Nanotechnology and Microengineering
/ Tumors
/ Valency
