Complement System: a Neglected Pathway in Immunotherapy.
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.
['Bordron|Anne|A|', 'Bagacean|Cristina|C|', 'Tempescul|Adrian|A|', 'Berthou|Christian|C|', 'Bettacchioli|Eléonore|E|', 'Hillion|Sophie|S|', 'Renaudineau|Yves|Y|http://orcid.org/0000-0001-5098-5002']
D000818:Animals D000911:Antibodies, Monoclonal D015415:Biomarkers D003167:Complement Activation D003170:Complement Pathway, Alternative D003171:Complement Pathway, Classical D003165:Complement System Proteins D006801:Humans D007155:Immunologic Factors D007167:Immunotherapy D016896:Treatment Outcome
Complement Monoclonal antibody Autoimmunity cancer