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Programmable multispecific DNA-origami-based T-cell engagers.
Nat. Nanotechnol. 18, 1319-1326 (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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Folding Dna; Nanostructures; Antibodies; Nanorobot
ISSN (print) / ISBN
1748-3387
e-ISSN
1748-3395
Journal
Nature Nanotechnology
Quellenangaben
Volume: 18,
Issue: 11,
Pages: 1319-1326
Publisher
Nature Publishing Group
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Unit for Clinical Pharmacology (KKG-EKLiP)
Grants
Deutsche Forschungsgemeinschaft (DFG)
Medical Valley Award
GO-Bio initial award (Federal Ministry of Education and Research (BMBF) of Germany) a
ForTra gGmbH fuer Forschungstransfer der Else Kroener-Fresenius Stiftung
Max Planck School Matter to Life - Federal Ministry of Education and Research (BMBF) of Germany
Max Planck Society
Bavarian Academy of Science
international doctoral program the Foerderprogramm fuer Forschung und Lehre der Medizinischen Fakultaet der LMU
DFG
Elite Network of Bavaria
Melanoma Research Alliance
Horizon 2020 programme of the European Union
Else Kroener-Fresenius-Stiftung
German Cancer Aid
Ernst Jung Stiftung
European Research Council Consolidator Grant
Institutional Strategy LMUexcellent of LMU Munich
Bundesministerium fuer Bildung und Forschung
European Research Council
Fritz-Bender Foundation
Deutsche Jose Carreras Leukaemie Stiftung
Hector Foundation
Wilhelm-Sander Stiftung
Medical Valley Award
GO-Bio initial award (Federal Ministry of Education and Research (BMBF) of Germany) a
ForTra gGmbH fuer Forschungstransfer der Else Kroener-Fresenius Stiftung
Max Planck School Matter to Life - Federal Ministry of Education and Research (BMBF) of Germany
Max Planck Society
Bavarian Academy of Science
international doctoral program the Foerderprogramm fuer Forschung und Lehre der Medizinischen Fakultaet der LMU
DFG
Elite Network of Bavaria
Melanoma Research Alliance
Horizon 2020 programme of the European Union
Else Kroener-Fresenius-Stiftung
German Cancer Aid
Ernst Jung Stiftung
European Research Council Consolidator Grant
Institutional Strategy LMUexcellent of LMU Munich
Bundesministerium fuer Bildung und Forschung
European Research Council
Fritz-Bender Foundation
Deutsche Jose Carreras Leukaemie Stiftung
Hector Foundation
Wilhelm-Sander Stiftung