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Scalable High Throughput Selection From Phage-displayed Synthetic Antibody Libraries
12:55

Scalable High Throughput Selection From Phage-displayed Synthetic Antibody Libraries

Published on: January 17, 2015

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Structure-guided phage display discovery of antibodies for (S)Tn-glycans in protein context

Ramon Hurtado-Guerrero1,2,3, Spyridon Gatos4, Irene Ginés-Alcober5

  • 1Institute of Biocomputation and Physics of Complex Systems, University of Zaragoza, Campus Rio Ebro, Zaragoza, Spain. rhurtado@bifi.es.

Nature Chemical Biology
|August 1, 2025
PubMed

Insights

Researchers developed a new method to create high-affinity monoclonal antibodies (mAbs) targeting cancer-specific carbohydrate antigens. This approach enhances specificity for tumor-associated glycan-peptide epitopes, improving cancer therapy potential.

Area of Science:

  • Immunology
  • Glycobiology
  • Cancer Research

Background:

  • Developing high-affinity monoclonal antibodies (mAbs) against tumor-associated carbohydrate antigens (Tn and STn) is crucial for cancer therapy but remains challenging.
  • These antigens, present as glycan-peptide epitopes (combotopes), demand precise recognition for high specificity.
  • Structural studies revealed distinct recognition roles for antibody VH (glycan) and VL (peptide) domains.

Purpose of the Study:

  • To develop a platform for generating highly specific monoclonal antibodies against tumor-associated carbohydrate antigens.
  • To leverage structural insights for designing antibodies with combotope-binding capabilities.
  • To engineer existing antibodies for altered specificity against different glycoforms.

Main Methods:

  • Creation of a VH-focused and VL-diverse phage display library.
  • Utilizing structural analysis to guide antibody engineering, specifically modifying VH complementarity-determining region 3.
  • Testing antibody specificity and affinity against glycoprotein targets MUC1 and CD43.

Main Results:

  • Discovery of mAbs with high specificity and affinity for combotopes.
  • Successful conversion of Tn-specific mAbs to STn-specific mAbs through targeted VH modification.
  • Validation of the platform using MUC1 and CD43 targets.

Conclusions:

  • The developed platform effectively addresses the challenge of generating glycoform-specific antibodies.
  • Engineered antibodies demonstrate potential for targeted cancer therapy, including antibody-drug conjugates due to efficient tumor cell uptake.
  • This approach offers a versatile strategy for discovering and optimizing antibodies against complex tumor-associated antigens.

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