Complement System: a Neglected Pathway in Immunotherapy

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.
Document type :
Journal articles
Complete list of metadatas

https://hal.univ-brest.fr/hal-02147331
Contributor : Geneviève Michel <>
Submitted on : Tuesday, June 4, 2019 - 3:55:39 PM
Last modification on : Wednesday, June 5, 2019 - 1:34:56 AM

Identifiers

Collections

Citation

Anne Bordron, Cristina Bagacean, Adrian Tempescul, Christian Berthou, Eléonore Bettachioli, et al.. Complement System: a Neglected Pathway in Immunotherapy. Clinical Reviews in Allergy and Immunology, Humana Press, 2019, ⟨10.1007/s12016-019-08741-0⟩. ⟨hal-02147331⟩

Share

Metrics

Record views

32