Complement-dependent toxicity

Complement-dependent cytotoxicity refers to the ability of therapeutic antibodies to kill cells to which they bind in a targeted manner without the aid of an effector cell (Peña JR et al. 2013).

Antibodies are able to kill cells in different ways. Antibodies which have developed the Fc portion of human IgG1 can develop complement dependent toxicity (cytotoxicity) which can lead to complement mediated cell death. A tubular membrane attack complex forms via a complement cascade, which forms a transmembrane channel (pore) of approximately 10 nm diameter in the target cell. This pore interferes with the selective permeability of the cell membrane. An unhindered exchange of water and electrolytes between the cell interior and the cell environment can take place. This ultimately leads to cytolysis and thus to the death of the cell(apoptosis).

The essential difference to ADCC, the antibody-dependent cell-mediated cytotoxicity, is that complement dependent toxicity involves the destruction of the target cell without the aid of an effector cell . Instead, the complement system is activated. ADCC and CDC are linked at the protein level and can influence each other. It is still unclear whether the mutual influences are predominantly inhibitory or reinforcing.

ADCC and CDC are used in oncological therapeutic approaches involving monoclonal antibodies, for example in rituximab - an anti-CD20 antibody used in the treatment of non-Hodgkin's lymphomas.

1. Duensing TD et al (2018) Complement-Dependent Cytotoxicity Assay. Cold Spring Harb Protoc: 10.1101/pdb.prot093799.