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Complement System: a Neglected Pathway in Immunotherapy

  • Anne Bordron
  • Cristina Bagacean
  • Adrian Tempescul
  • Christian Berthou
  • Eléonore Bettacchioli
  • Sophie Hillion
  • Yves RenaudineauEmail author
Article

Abstract

Approved for the treatment of autoimmune diseases, hematological malignancies, and solid cancers, several monoclonal antibodies (mAb) make use of complement in their mechanism of action. Such an assessment is based on comprehensive investigations that used mouse models, in vitro studies, and analyses from patients at initiation (basal level to highlight deficiencies) and after treatment initiation (mAb impact on complement), which have further provided key insights into the importance of the complement activation and/or complement deficiencies in mAb activity. Accordingly, new approaches can now be developed with the final objective of increasing the clinical efficacy of mAb. These improvements include (i) the concurrent administration of fresh frozen plasma during mAb therapy; (ii) mAb modifications such as immunoglobulin G subclass switching, Fc mutation, or IgG hexamerization to improve the fixation and activation of C1q; (iii) optimization of the target recognition to induce a higher complement-dependent cytotoxicity (CDC) and/or complement-dependant cellular cytotoxicity (CDCC); and (iv) the control of soluble and cellular complement inhibitors.

Keywords

Monoclonal antibody Complement Autoimmunity cancer 

Notes

Acknowledgments

We are thankful to Servier Medical for providing free art for the figures, and Genevieve Michel for secretarial help.

Funding

This study was supported by the “Ligue against cancer”, the Brittany region, and the Brest University Hospital INNOVEO donation fund.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Inserm UMR1227, B lymphocytes and autoimmunityUniversity of BrestBrestFrance
  2. 2.Service d’HématologieCHU de BrestBrestFrance
  3. 3.Laboratory of Immunology and ImmunotherapyCHU de BrestBrestFrance

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