Novel protein scaffolds as emerging therapeutic proteins: from discovery to clinical proof-of-concept

Recent advances in combinatorial protein engineering have made it possible to develop immunoglobulin (Ig)-based and non-Ig protein scaffolds that can potentially substitute for most whole antibody-associated properties and currently translate into biologicals with drug-like properties. During the past 10 years, the most validated scaffolds have reached the clinical development phase and, recently, one of them [Kalbitor® (Dyax)] has made it to the market, making these alternative scaffold proteins viable drug candidates in a post-antibody landscape. Interestingly, several scaffolds include an immune-active component as part of their therapeutic mode of action, which yielded spectacular clinical efficacy in some hematological malignancies. Here, we review the most recent clinical advances and analyze their benefits for patients.