Antibody-drug conjugates

Abstract

Monoclonal Antibodies (MAbs) belong among the fastest growing types of biologics for a variety of different indications and employing different mechanisms of action. The trend in the development of new MAbs is to modify their basic structure, leading to an improvement in the therapeutic profile or at least pharmacokinetic properties. In addition to the basic types of antibodies, their biosynthetic and semi-synthetic modifications are currently available for clinical use. Biosynthetic interventions include e.g. changes in the sugar moiety of the molecule, or the changes of several amino acids in constant regions of the MAb. Variable antibody fragments alone, either free or with 20–40 kDa polyethylene glycol units, are also used. Of the semi-synthetic variants, the most used one is the preparation of Antibody-Drug Conjugates (ADC) where the antibody, in addition to its own biological activity, has primarily the function of a transporting tools. The conjugated molecules or particles typically have cytotoxic activity and thus increase the efficiency of the antibody by another additional mechanism, selectively only to cells carrying the target antigen. Complexing molecules, subsequently bearing a radionuclide, as well as bacterial or plant toxin can also be conjugated.