Albumin is the most abundant protein in serum and acts as a multifunctional carrier for many endogenous small molecules, as diverse as fatty acids, metals, bilirubin, amino acids, and vitamins that ensure wide biodistribution of these compounds throughout the body. In addition, its remarkably long half-life of 19 days in humans makes albumin a versatile and preferred carrier for small molecule and protein therapeutics. A receptor-mediated pathway controlled by the neonatal Fc receptor (FcRn) has recently been shown to be essential for regulation of the long half-life of albumin as well as IgG. This new discovery will strongly influence the further development of albumin-fused and albumin-targeting diagnostics and therapeutics.

The IgG class has a remarkably long serum half-life of 21 days in humans. The utility of the mAbs spans across clinical settings such as treatment of cancer, chronic inflammatory and autoimmune diseases as well as transplantation and cardiovascular disease. Such treatments require large quantities of mAbs; a restriction that limits their use is the manufacturing cost in mammalian production systems. The most promising alternatives are production in yeast and bacteria of Ab derived fragments such as the Fab, F(ab′)2 and single-chain Fv (ScFv) (Figure 20.1A–C). These lack the Fc part and Fc-associated functions, which may be favorable when complement activation and FcγR-mediated effector functions are inconvenient. However, elimination of the Fc also removes the half-life extending mechanism mediated by interaction of Fc with FcRn.