Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment

Trends Pharmacol Sci. 2016 Dec;37(12):993-1008. doi: 10.1016/j.tips.2016.10.005. Epub 2016 Nov 9.

Abstract

Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity. In this review we highlight some of these strategies and provide examples of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer.

Keywords: biologics; biotherapeutics; oncology drugs; protein engineering; targeted therapies.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Biological Products / administration & dosage
  • Biological Products / pharmacology
  • Drug Design
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Protein Engineering / methods*
  • Proteins / administration & dosage
  • Proteins / pharmacology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Biological Products
  • Proteins