Multivalent Display of Single-Domain Antibodies

Antigen-binding fragments, such as single-domain antibodies (sdAbs), can now be readily isolated by in vitro technologies. Antibody fragment libraries derived from immune or nonimmune sources are presented in a molecular display format, typically phage display, and binders to individual antigens are selected from the libraries by a so-called panning process. Nonimmune libraries can serve as sources of binders to a wide range of targets but yield antigen-binding fragments that generally have much lower affinities than those obtained from immune sources. Here we describe a strategy for constructing pentameric sdAbs termed pentabodies. Pentamerization introduces avidity which can greatly enhance the binding of low affinity sdAbs to antigens presented on surfaces.