Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery

Trends Immunol. 2017 Jun;38(6):383-394. doi: 10.1016/ Epub 2017 Apr 14.


Complement dysregulation underlies several inflammatory disorders, and terminal complement inhibition has thus far afforded significant clinical gains. Nonetheless, emerging pathologies, fueled by complement imbalance and therapy-skewing genetic variance, underscore the need for more comprehensive, disease-tailored interventions. Modulation at the level of C3, a multifaceted orchestrator of the complement cascade, opens up prospects for broader therapeutic efficacy by targeting multiple pathogenic pathways modulated by C3-triggered proinflammatory crosstalk. Notably, C3 intervention is emerging as a viable therapeutic strategy for renal disorders with predominantly complement-driven etiology, such as C3 glomerulopathy (C3G). Using C3G as a paradigm, we argue that concerns about the feasibility of long-term C3 intervention need to be placed into perspective and weighed against actual therapeutic outcomes in prospective clinical trials.

Keywords: AMY-101; C3 glomerulopathy; C3 inhibitors; anti-C5 therapy; clinical efficacy; compstatin.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Blocking / therapeutic use
  • Clinical Trials as Topic
  • Complement Activation
  • Complement C3 / immunology
  • Complement C3 / metabolism*
  • Evidence-Based Medicine
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / immunology
  • Humans
  • Immune Complex Diseases / drug therapy*
  • Immune Complex Diseases / immunology
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Models, Immunological
  • Molecular Targeted Therapy


  • Antibodies, Blocking
  • Complement C3