High-affinity self-reactive human antibodies by design and selection: targeting the integrin ligand binding site.

• C F Barbas

  Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.

• L R Languino

  Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.

• J W Smith

  Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.

抄録

A strategy for the design and selection of human antibodies that bind receptors is described. We have demonstrated the validity of the approach by producing semi-synthetic human antibodies that bind integrins alpha v beta 3 and alpha IIb beta 3 with high affinity (10(-10) M). The selected antibodies mimic the integrins' natural ligands as demonstrated by their ability to compete with these ligands and Arg-Gly-Asp (RGD)-containing peptides for binding to the integrins. Furthermore, the antibodies bind in a cation-dependent fashion and are functional in cell adhesion assays. Antibodies that are high-affinity inhibitors of cell adhesion receptors should be of use in assessing receptor function and dissecting mechanisms of adhesion. Semisynthetic human antibodies that target integrins are potential therapeutic agents for the treatment of a number of diseases including thrombosis and metastasis. Furthermore, antibodies that are optimized to bind by a single complementarity determining region may be important lead compounds for the design of small molecule pharmaceuticals.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 90 (21), 10003-10007, 1993-11

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1361699995943911424
• NII論文ID: 30016294927
• DOI: 10.1073/pnas.90.21.10003
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.90.21.10003
• データソース種別:
  • Crossref
  • CiNii Articles