Generation of glycan-specific nanobodies

Sana Khan Khilji, Felix Goerdeler, Kristin Frensemeier, David Warschkau, Jost Lühle, Zeinab Fandi, Falko Schirmeister, Zhuo Angel Chen, Onur Turak, Alvaro Mallagaray, Stefan Boerno, Bernd Timmermann, Juri Rappsilber, Peter H. Seeberger, Oren Moscovitz

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)1353-1361.e6
Number of pages9
JournalCell Chemical Biology
Issue number8
Early online date14 Jun 2022
Publication statusPublished - 18 Aug 2022

Keywords / Materials (for Non-textual outputs)

  • nanobody
  • single domain antibody
  • heavy chain only antibody
  • glycan
  • glycoconjugate
  • immunization
  • globo H
  • tumor associated carbohydrate antigen
  • cancer
  • alpaca
  • active immunization


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