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RESEARCH PRODUCT
The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies.
Martina AnzagheSimone DudekZoe WaiblerGer Van ZandbergenGer Van ZandbergenPatricia Gogeschsubject
modes of action (MoA)GlycosylationQH301-705.5medicine.drug_classCellReceptors FcReviewBiologyMonoclonal antibodyCatalysisInorganic Chemistrychemistry.chemical_compoundMonoklonaler Antikörper ; effector function ; antibody dependent cellular phagocytosis (ADCP) ; therapeutic monoclonal antibodies (mAbs) ; Fcγ receptor (FcγR) ; modes of action (MoA) ; antibody dependent cellular cytotoxicity (ADCC)medicineAnimalsHumansAvidityClinical efficacyBiology (General)Physical and Theoretical ChemistryReceptorQD1-999Molecular BiologySpectroscopyAntibody-dependent cell-mediated cytotoxicityEffectortherapeutic monoclonal antibodies (mAbs)Organic ChemistryAntibody-Dependent Cell CytotoxicityAntibodies Monoclonalantibody dependent cellular phagocytosis (ADCP)General MedicineFcγ receptor (FcγR)Computer Science ApplicationsImmunoglobulin Fc Fragmentsantibody dependent cellular cytotoxicity (ADCC)Chemistrymedicine.anatomical_structurechemistryImmunologyImmunotherapyeffector functiondescription
Since the approval of the first monoclonal antibody (mAb) in 1986, a huge effort has been made to guarantee safety and efficacy of therapeutic mAbs. As of July 2021, 118 mAbs are approved for the European market for a broad range of clinical indications. In order to ensure clinical efficacy and safety aspects, (pre-)clinical experimental approaches evaluate the respective modes of action (MoA). In addition to antigen-specificity including binding affinity and -avidity, MoA comprise Fc-mediated effector functions such as antibody dependent cellular cytotoxicity (ADCC) and the closely related antibody dependent cellular phagocytosis (ADCP). For this reason, a variety of cell-based assays have been established investigating effector functions of therapeutic mAbs with different effector/target-cell combinations and several readouts including Fcγ receptor (FcγR)-mediated lysis, fluorescence, or luminescence. Optimized FcγR-mediated effector functions regarding clinical safety and efficacy are addressed with modification strategies such as point mutations, altered glycosylation patterns, combination of different Fc subclasses (cross isotypes), and Fc-truncation of the mAb. These strategies opened the field for a next generation of therapeutic mAbs. In conclusion, it is of major importance to consider FcγR-mediated effector functions for the efficacy of therapeutic mAbs.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-08-01 | International journal of molecular sciences |