Programmable multispecific DNA-origami-based T-cell engagers

Klaus F. Wagenbauer, Nhi Pham, Adrian Gottschlich, Benjamin Kick, Viktorija Kozina, Christopher Frank, Daniela Trninic, Pierre Stömmer, Ruth Grünmeier, Emanuele Carlini, Christina Angeliki Tsiverioti, Sebastian Kobold, Jonas J. Funke & Hendrik Dietz

Nature Nanotechnology (2023).

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.

About Lulu Qian (54 Articles)
President of ISNSCE Professor of Bioengineering California Institute of Technology