Intein mediated high throughput screening for bispecific antibodies.

MAbs
Tim HofmannAchim Doerner

Abstract

Bispecific antibodies comprise extremely diverse architectures enabling complex modes of action, such as effector cell recruitment or conditional target modulation via dual targeting, not conveyed by monospecific antibodies. In recent years, research on bispecific therapeutics has substantially grown. However, evaluation of binding moiety combinations often leads to undesired prolonged development times. While high throughput screening for small molecules and classical antibodies has evolved into a mature discipline in the pharmaceutical industry, dual-targeting antibody screening methodologies lack the ability to fully evaluate the tremendous number of possible combinations and cover only a limited portion of the combinatorial screening space. Here, we propose a novel combinatorial screening approach for bispecific IgG-like antibodies to extenuate screening limitations in industrial scale, expanding the limiting screening space. Harnessing the ability of a protein trans-splicing reaction by the split intein Npu DnaE, antibody fragments were reconstituted within the hinge region in vitro. This method allows for fully automated, rapid one-pot antibody reconstitution, providing biological activity in several biochemical and funct...Continue Reading

References

Feb 19, 2000·Current Opinion in Biotechnology·S A Sundberg
May 17, 2003·Nature Reviews. Drug Discovery·Konrad H BleicherAlexander I Alanine
Nov 30, 2004·Science·Eric VivierFrédéric Vély
Jul 19, 2006·Drug Discovery Today·Ge Wu, Stephen K Doberstein
Sep 16, 2006·Journal of Biomolecular Screening·Sandra FoxMichael Biros
May 23, 2009·British Journal of Pharmacology·Patrick ChamesDaniel Baty
Jun 11, 2009·Cancer Research·Patrick A Baeuerle, Carsten Reinhardt
Sep 25, 2009·Current Opinion in Pharmacology·Lorenz M Mayr, Dejan Bojanic
Apr 5, 2011·Experimental Cell Research·John R Desjarlais, Greg A Lazar
Jul 4, 2012·The Journal of Biological Chemistry·Patricia Carvajal-VallejosStefan R Schmidt
Dec 26, 2012·Journal of the American Chemical Society·Miquel Vila-PerellóTom W Muir
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Aran F LabrijnPaul W H I Parren
Mar 20, 2013·Journal of the American Chemical Society·Neel H ShahTom W Muir
Apr 5, 2014·The Journal of Biological Chemistry·David W Wood, Julio A Camarero
Nov 2, 2014·Nature Reviews. Drug Discovery·Ken Garber
Mar 3, 2015·Drug Discovery Today·Roland E Kontermann, Ulrich Brinkmann
Aug 13, 2015·Immunobiology·Jens Pahl, Adelheid Cerwenka
Feb 9, 2016·Journal of the American Chemical Society·Adam J StevensTom W Muir
Dec 17, 2016·Electrophoresis·Bernd Moritz, Jan Olaf Stracke
Jan 8, 2017·Protein Engineering, Design & Selection : PEDS·Simon KrahStefan Becker
Jan 11, 2017·MAbs·Ulrich Brinkmann, Roland E Kontermann
May 19, 2017·Therapeutic Advances in Vaccines·Kuang-Yuh ChyuPrediman K Shah
Dec 2, 2017·Nature Reviews. Drug Discovery·Paul J Carter, Greg A Lazar
Aug 23, 2018·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Bushra Husain, Diego Ellerman
Oct 12, 2018·Methods : a Companion to Methods in Enzymology·Lei HanJianwei Zhu
Nov 20, 2018·Methods : a Companion to Methods in Enzymology·Christian KleinPablo Umaña
Jun 9, 2019·Nature Reviews. Drug Discovery·Aran F LabrijnPaul W H I Parren
Oct 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·Maniraj BhagawatiHenning D Mootz

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Citations

Sep 12, 2020·International Journal of Molecular Sciences·Tim HofmannAchim Doerner
Dec 29, 2020·Bioorganic & Medicinal Chemistry·Jisoo ParkTae Hyeon Yoo
Feb 3, 2021·Cell Chemical Biology·Christian HentrichFrancisco Ylera
Oct 16, 2020·International Journal of Molecular Sciences·Manali S SawantPeter M Tessier

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Methods Mentioned

BETA
electrophoresis
biolayer interferometry
biosensors
thermal shift
flow cytometry
enzyme-linked immunosorbent assay
ELISA
flow
transfection
size exclusion chromatography

Software Mentioned

GraphPad Prism
BiomekFX
LabChip GX Reviewer
ForteBio
LabChip GX

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