Skip to main content
. 2020 Nov 1;21(21):8192. doi: 10.3390/ijms21218192

Figure 1.

Figure 1

Monoclonal antibodies: types and mechanisms of action. (a) Naked monoclonal antibody (mAb). Antibody-dependent cellular cytotoxicity (ADCC): natural killer cell (NK) binds to the Fc region via the Fc-receptor and releases lytic factors such as perforin and granzymes. Complement-dependent cytotoxicity (CDC): interaction between the Fc region and protein C1q activates the classic complement pathway that results in the formation of membrane attack complex (MAC) and cell lysis. Antibody-dependent phagocytosis (ADP): the binding of macrophages induces activation of phagocytosis. Direct effects: induction of apoptosis directly or through cross-linking; effects depending on specific antigen functions (e.g., inhibition of intracellular signaling, blocking of enzymatic functions). Checkpoint inhibitors: blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte antigen 4 (CTLA-4) preventing immune response suppression. Immunomodulation: interaction of mAb with stroma cells, which inhibit T cell activation restoring the immune response against neoplastic cells. (b) Antibody–drug conjugate. Upon antibody binding to the target, a cytotoxic payload is released in the target cell. (c) Bispecific monoclonal antibodies. Ig-like: two binding sites with different specificity and an Fc region that binds to the Fc-receptor. Non-Ig-like: two different single-chain variable fragments (variable regions comprised only of the variable regions of the heavy and light chains). Bispecific monoclonal antibodies usually bind a tumor antigen and an immune effector antigen (e.g., CD3 on the T-cell surface), in order to activate the immune cells against the neoplastic cell. Abbreviations: +/++/+++, low/moderate/high; Fab, fragment antigen binding; FC, fragment crystallizable region; Treg, regulatory T cell; MDSC, myeloid-derived suppressor cell; NK, natural killer cell; ADCC, antibody-dependent cellular cytotoxicity; CDC, complement-dependent cytotoxicity; MAC, membrane attack complex; ADP, antibody-dependent phagocytosis; APC, antigen-presenting cell; ADCs, antibody–drug conjugates; BiAbs, bispecific antibodies; CTLA-4, cytotoxic T-lymphocyte antigen 4; PD-1, programmed cell death protein 1; PD-L1, programmed death ligand 1; di-scFv, bivalent single-chain variable fragment; scFv, single-chain variable fragment; CRS: cytokine release syndrome; Ig, immunoglobulin.