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Review

Greatest Hits—Innovative Technologies for High Throughput Identification of Bispecific Antibodies

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Advanced Cell Culture Technologies, Merck Life Sciences KGaA, Frankfurter Strasse 250, D-64293 Darmstadt, Germany
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Protein Engineering and Antibody Technologies, Merck Healthcare KGaA, Frankfurter Strasse 250, D-64293 Darmstadt, Germany
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6551; https://doi.org/10.3390/ijms21186551
Received: 4 August 2020 / Revised: 3 September 2020 / Accepted: 4 September 2020 / Published: 8 September 2020
(This article belongs to the Special Issue Monoclonal Antibodies to Treat Cancer)
Recent years have shown a tremendous increase and diversification in antibody-based therapeutics with advances in production techniques and formats. The plethora of currently investigated bi- to multi-specific antibody architectures can be harnessed to elicit a broad variety of specific modes of actions in oncology and immunology, spanning from enhanced selectivity to effector cell recruitment, all of which cannot be addressed by monospecific antibodies. Despite continuously growing efforts and methodologies, the identification of an optimal bispecific antibody as the best possible combination of two parental monospecific binders, however, remains challenging, due to tedious cloning and production, often resulting in undesired extended development times and increased expenses. Although automated high throughput screening approaches have matured for pharmaceutical small molecule development, it was only recently that protein bioconjugation technologies have been developed for the facile generation of bispecific antibodies in a ‘plug and play’ manner. In this review, we provide an overview of the most relevant methodologies for bispecific screening purposes—the DuoBody concept, paired light chain single cell production approaches, Sortase A and Transglutaminase, the SpyTag/SpyCatcher system, and inteins—and elaborate on the benefits as well as drawbacks of the different technologies. View Full-Text
Keywords: bispecific antibodies; high throughput screening; protein trans splicing; inteins; DuoBodies; controlled Fab-arm exchange; Sortase A; microbial transglutaminase; SpyTag; SpyCatcher bispecific antibodies; high throughput screening; protein trans splicing; inteins; DuoBodies; controlled Fab-arm exchange; Sortase A; microbial transglutaminase; SpyTag; SpyCatcher
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MDPI and ACS Style

Hofmann, T.; Krah, S.; Sellmann, C.; Zielonka, S.; Doerner, A. Greatest Hits—Innovative Technologies for High Throughput Identification of Bispecific Antibodies. Int. J. Mol. Sci. 2020, 21, 6551. https://doi.org/10.3390/ijms21186551

AMA Style

Hofmann T, Krah S, Sellmann C, Zielonka S, Doerner A. Greatest Hits—Innovative Technologies for High Throughput Identification of Bispecific Antibodies. International Journal of Molecular Sciences. 2020; 21(18):6551. https://doi.org/10.3390/ijms21186551

Chicago/Turabian Style

Hofmann, Tim, Simon Krah, Carolin Sellmann, Stefan Zielonka, and Achim Doerner. 2020. "Greatest Hits—Innovative Technologies for High Throughput Identification of Bispecific Antibodies" International Journal of Molecular Sciences 21, no. 18: 6551. https://doi.org/10.3390/ijms21186551

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