Beyond antibodies: using biological principles to guide the development of next-generation protein therapeutics

MS Kariolis, S Kapur, JR Cochran - Current opinion in biotechnology, 2013 - Elsevier
MS Kariolis, S Kapur, JR Cochran
Current opinion in biotechnology, 2013Elsevier
Highlights•Biologics based on monoclonal antibodies have dominated the clinical
landscape.•New knowledge of disease mechanisms is driving current drug discovery
efforts.•Ligands and receptors provide unique opportunities to manage biological
complexity.•Protein engineering is generating therapeutics with improved safety and
efficacy.Protein-based biologics, which leverage the inherent affinity and specificity of
protein–protein interactions, offer an effective strategy for targeting and modulating disease …
Highlights
  • Biologics based on monoclonal antibodies have dominated the clinical landscape.
  • New knowledge of disease mechanisms is driving current drug discovery efforts.
  • Ligands and receptors provide unique opportunities to manage biological complexity.
  • Protein engineering is generating therapeutics with improved safety and efficacy.
Protein-based biologics, which leverage the inherent affinity and specificity of protein–protein interactions, offer an effective strategy for targeting and modulating disease pathways. Despite the broad diversity of the proteome, monoclonal antibodies have been the major focus of such drug discovery efforts. While antibodies have shown great clinical value, the breadth and complexity of human disease highlight the need for alternatives that expand the therapeutic repertoire beyond this single class of proteins. The elucidation of molecular mechanisms underlying human disease has provided new opportunities for protein-based drugs to address challenging clinical problems. Natural ligands and receptors, which inherently modulate complex biological processes, have emerged as promising candidates for protein-based drug discovery efforts. Protein engineering strategies, guided by biological principles, are allowing ligands and receptors to be developed as next-generation therapeutics with improved safety and efficacy.
Elsevier