Benefit from the unique properties of therapeutic antibodies
Therapeutic antibodies are a rapidly evolving class of drugs that has been gaining ground over small molecules for the treatment of cancer, autoimmune diseases, and reversal of drug effects. Their success in the clinic stems from their ability to engage specific targets (i.e. antigens) through their antigen-binding region (Fab) and, at the same time, activate the organism’s immune response through their crystallizable region (Fc).
Most therapeutic antibodies in clinical use are humanized or human monoclonal molecules (mAbs). These molecules are typically generated through hybridomas in mice or transgenic mice (harboring human antibody genes) or phage display of vast antibody libraries (naïve, immune, semi-synthetic, or synthetic libraries).
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These mAbs can be classified according to the effector functions they can trigger. For instance, they can block specific pathogens or pathophysiological pathways. In this case, these therapeutic antibodies are termed neutralizing. Antibodies can also be designed to recruit specific cytotoxic cells (i.e. macrophages and natural killer cells), triggering the so-called antibody-dependent cell-mediated cytotoxic (ADCC) activity. Additionally, mAbs can trigger a cascade of complement proteins that lead the production of a complex that, in turn, triggers the lysis of the targeted cell. This mechanism is known as the complement-dependent cytotoxic (CDC) activity.
Most therapeutic antibodies, especially the ones developed for cancer, can trigger more than one type of immune response (neutralizing, ADCC, an CDC) in patients. The type of the effector function an antibody can trigger heavily depends on the glycosylation patterns of the Fc regions.
Glycans can cause significant differences in conformation, which results in changes in antibody affinity and the ability to activate the complement system. For this reason, the efficiency of therapeutic antibodies depends on the recombinant expression system used to produce them. For many years, CHO (Chinese hamster ovary) cells have been the most important mammalian cell lines used in therapeutic antibody production. They are prized for their ability to produce mAbs with human-like glycosylation, crucial to trigger essential effector responses in the human organism.