The emerging role of new protein scaffold-based agents for treatment of cancer

Abstract

In order to overcome limitations of monoclonal antibodies, new protein-based scaffolds have been designed and evaluated pre-clinically, and some of them are in clinical studies for the treatment of cancer. These entities can be placed into two categories: scaffolds which bind ligands via amino acids in exposed loops and those in which ligand binding is mediated by amino acids in secondary structures, such as β-sheet modules. Accordingly, we discuss adnectins, lipocalins, Kunitz domain-based binders, avimers, knottins, fynomers, atrimers and cytotoxic T-lymphocyte associated protein-4 (CTLA4)-based binders which fall into the first category, while darpins, affibodies, affilins and armadillo repeat protein-based scaffolds are members of the second category. In addition, we also discuss the new molecular entities as imaging tools and outline their unique characteristics in the context of multimeric and multivalent binding.

Keywords: Angiogenesis; HER signaling; multivalent; extension of plasma half-life; multispecific; phage and ribosome display; pharmacokinetics; randomisation of loops and β sheets; review.