New concepts on the therapeutic control of complement anaphylatoxin receptors

Mol Immunol. 2017 Sep:89:36-43. doi: 10.1016/j.molimm.2017.05.015. Epub 2017 May 30.


The complement system is a pivotal driver of innate immunity, coordinating the host response to protect against pathogens. At the heart of the complement response lie the active fragments, C3a and C5a, acting through their specific receptors, C3aR, C5aR1, and C5aR2, to direct the cellular response to inflammation. Their potent function however, places them at risk of damaging the host, with aberrant C3a and C5a signaling activity linked to a wide range of disorders of inflammatory, autoimmune, and neurodegenerative etiologies. As such, the therapeutic control of these receptors represents an attractive drug target, though, the realization of this clinical potential remains limited. With the success of eculizumab, and the progression of a number of novel C5a-C5aR1 targeted drugs to phase II and III clinical trials, there is great promise for complement therapeutics in future clinical practice. In contrast, the toolbox of drugs available to modulate C3aR and C5aR2 signaling remains limited, however, the emergence of new selective ligands and molecular tools, and an increased understanding of the function of these receptors in disease, has highlighted their unique potential for clinical applications. This review provides an update on the growing arsenal of drugs now available to target C5, and C5a and C3a receptor signaling, and discusses their utility in both clinical and pre-clinical development.

Keywords: C3a receptor; C5a; C5a receptor; Complement; Inflammation; Therapeutics.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Complement Activation / drug effects
  • Complement Activation / immunology*
  • Complement C3a / immunology*
  • Complement C5a / immunology*
  • Complement Inactivating Agents / therapeutic use
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Receptor, Anaphylatoxin C5a / immunology*
  • Receptors, Chemokine / immunology*
  • Receptors, Complement / immunology*


  • Antibodies, Monoclonal, Humanized
  • C5AR1 protein, human
  • C5aR2 protein, human
  • Complement Inactivating Agents
  • Receptor, Anaphylatoxin C5a
  • Receptors, Chemokine
  • Receptors, Complement
  • complement C3a receptor
  • Complement C3a
  • Complement C5a
  • eculizumab