1. [Protein scaffolds as alternatives to whole antibodies: from discovery research to clinical development].
- Author
-
Wurch T, Lowe P, Beck A, and Corvaia N
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal chemistry, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Antibodies, Antineoplastic Agents chemistry, Antineoplastic Agents therapeutic use, Biopolymers, Clinical Trials as Topic, Drug Design, Drug Screening Assays, Antitumor, Fibronectins chemistry, Fibronectins therapeutic use, Humans, Inflammation drug therapy, Mice, Mice, Nude, Models, Molecular, Neoplasms drug therapy, Neovascularization, Pathologic drug therapy, Peptide Fragments therapeutic use, Peptides chemistry, Peptides therapeutic use, Protein Conformation, Protein Engineering, Protein Structure, Tertiary, Receptors, LDL chemistry, Receptors, LDL therapeutic use, Staphylococcal Protein A chemistry, Staphylococcal Protein A therapeutic use, Structure-Activity Relationship, Peptide Fragments chemistry
- Abstract
Recent advances in combinatorial protein engineering have made it possible to develop non-Ig protein scaffolds that can potentially substitute for most whole antibody-associated properties. These protein scaffolds display most of the binding properties associated with the variable domain of antibodies. In theory, many different natural human protein backbones are suitable to be used as recombinant templates for engineering ; in practice however, only a few have yielded the necessary properties to be translated into << druggable biologicals >>. Amongst these properties, potential broad specificities towards any kind of target, ease of production, small size, good tolerability and low immunogenicity are essential. Intellectual property is another key issue. In this review, a particular emphasis will be given to the most validated non-Ig scaffolds that have reached the clinical development phase.
- Published
- 2009
- Full Text
- View/download PDF