FUNCTIONAL AND PHARMACOKINETIC PROPERTIES OF ANTIBODY-AVIDIN FUSION PROTEINS

In an attempt to produce broadly useful targeting agents, genetic engi neering and expression techniques have been used to produce Ab-avidin fusion proteins. Chicken avidin has been fused to mouse-human chimeric IgG3 at the end of C(H)1 (C(H)1-Av), immediately after the hinge (H-A v), and at the end of C(H)3 (C(H)3-Av). Fusion heavy chains of the exp ected molecular mass were expressed, assembled with a co-expressed rig ht chain, and secreted. The resulting molecules continued to bind Ag. They also bound biotinylated human serum albumin; C(H)3-Av had reduced affinity (K-A = 5.13 x 10(9) M-1) compared with the tetrameric avidin (K-A = 1 x 10(15) M-1), but greater affinity than monomeric avidin (K -A = 1 x 10(7) M-1). Importantly, the avidin-IgG fusion proteins had a longer serum t(1/2) in rats than avidin. The favorable pharmacokineti c parameters suggest that these avidin fusion proteins can be used eff ectively to deliver biotinylated ligands such as drugs and peptides to locales expressing any Ag recognized by the associated Ab.