Single Domain Human Immunoglobulin Fold-Based Biomolecules

Single domain human immunoglobulin fold-based biomolecules Simon E. Hufton Target Quest B.V., University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands We have developed human immunoglobulin fold containing proteins as alternative binding ligands to antibodies. Firstly, we have evaluated cytotoxic T lymphocyte associated antigen 4 (CTLA-4) as a protein scaffold. CTLA-4 is an important regulator of cellular immunity and is transiently expressed on the surface of T cells. To have a suitable library selection system we have displayed the extracellular domain of CTLA-4 in 1A subsidiary of Dyax Corp. a functional form on the surface of filamentous phage. We have generated both engineered CTLA-4 variants and repertoires of CTLA-4 variants from which binding ligands to somatostatin receptors and αvβ3 integrin have been isolated. We have also investigated the potential of single VL domains as binding ligands From a naı̈ve repertoire, single VL domains were isolated which were able to bind to B7-1 and B7-2 which are important costimulatory molecules on antigen presenting cells. We believe that these monomeric immunoglobulins may present certain advantages over classical antibodies for certain applications. Disease Markers 16 (2000) 37 ISSN 0278-0240 / $8.00  2000, IOS Press. All rights reserved