Recombinant therapeutic monoclonal antibodies: mechanisms of action in relation to structural and functional duality.
Naked therapeutic recombinant monoclonal antibodies (mAbs) are bifunctional molecules. On the one hand, they recognize their antigen through the variable regions of the antigen binding portion (Fab). The recombinant mAb binding to a soluble or a membrane antigen may interfere with one or several functions of this antigen, leading to the therapeutic effect. On the other hand, since their crystalisable portion (Fc) is humanized (usually IgG1), they interact efficiently with human Fc-binding molecules, such as C1q and receptors for the Fc portion of IgG (FcgammaR). Thus, they initiate the classical pathway of complement and activate FcgammaR-expressing cells. The recruitment of these patient immune effector functions is essential in the therapeutic effect of several recombinant mAbs used in oncology. The aim of this review is to describe the main mechanisms of action of recombinant mAbs in relation to this structural and functional duality.
Congy-Jolivet
Nicolas
N
Université François Rabelais de Tours, EA 3853 Immuno-Pharmaco-Génétique des Anticorps thérapeutiques, 10 Boulevard Tonnellé, 37032 Tours Cedex, France.
Probst
Alicia
A
Watier
Hervé
H
Thibault
Gilles
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000502:physiology / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000502:physiology; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000502:physiology; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000737:chemistry* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D011994:Recombinant Proteins