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  Generation of glycan-specific nanobodies

Khilji, S. K., Goerdeler, F., Frensemeier, K., Warschkau, D., Lühle, J., Fandi, Z., et al. (2022). Generation of glycan-specific nanobodies. Cell Chemical Biology. doi:10.1016/j.chembiol.2022.05.007.

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Khilji, Sana K.1, Author              
Goerdeler, Felix1, Author              
Frensemeier, Kristin1, Author
Warschkau, David1, Author
Lühle, Jost1, Author              
Fandi, Zeinab1, Author
Schirmeister, Falko2, Author              
Chen, Zhuo Angel, Author
Turak, Onur, Author
Mallagaray, Alvaro, Author
Boerno, Stefan, Author
Timmermann, Bernd, Author
Rappsilber, Juri, Author
Seeberger, Peter H.3, Author              
Moscovitz, Oren1, Author              
Affiliations:
1Oren Moscovitz, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_3176803              
2Daniel Kolarich, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863301              
3Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              

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Free keywords: nanobody; single-domain antibody; heavy chain-only antibody; glycan; glycoconjugate; immunization; Globo-H; tumor-associated carbohydrate antigen; cancer; alpaca; active immunization
 Abstract: The development of antibodies that target specific glycan structures on cancer cells or human pathogens poses a significant challenge due to the immense complexity of naturally occurring glycans. Automated glycan assembly enables the production of structurally homogeneous glycans in amounts that are difficult to derive from natural sources. Nanobodies (Nbs) are the smallest antigen-binding domains of heavy-chain-only antibodies (hcAbs) found in camelids. To date, the development of glycan-specific Nbs using synthetic glycans has not been reported. Here, we use defined synthetic glycans for alpaca immunization to elicit glycan-specific hcAbs, and describe the identification, isolation, and production of a Nb specific for the tumor-associated carbohydrate antigen Globo-H. The Nb binds the terminal fucose of Globo-H and recognizes synthetic Globo-H in solution and native Globo-H on breast cancer cells with high specificity. These results demonstrate the potential of our approach for generating glycan-targeting Nbs to be used in biomedical and biotechnological applications.

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Language(s): eng - English
 Dates: 2022-06-14
 Publication Status: Published online
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 Identifiers: DOI: 10.1016/j.chembiol.2022.05.007
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Title: Cell Chemical Biology
Source Genre: Journal
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Publ. Info: Cell Press
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 2451-9456