FUNCTIONAL-PROPERTIES OF ANTIBODY INSULIN-LIKE GROWTH-FACTOR FUSION PROTEINS

Genetic engineering and expression techniques have been used to produc e antibody growth factor fusion proteins. Insulin-like growth factors (IGFs) 1 and 2 have been fused to mouse human chimeric IgG3 at the end of C(H)1, immediately after the hinge, and at the end of C(H)3. Fusio n heavy chains of the expected molecular weight were expressed, assemb led with a co-expressed light chain, and secreted. The resulting molec ules continued to bind antigen; they also bound the growth factor rece ptors, albeit with decreased affinity. The molecule with IGF1 attached after C(H)3 (CH3-IGF1) had reduced ability to carry out complement-me diated cytolysis. In contrast the molecule with IGFS attached after C( H)3 (C(H)3-IGF2) showed an approximately 50-fold increase in its abili ty to effect complement-mediated cytolysis and so should be an effecti ve cytolytic agent. Both C(H)3-IGF1 and C(H)3-IGF2 bound Fc gamma RI w ith affinity similar to that of IgG3. The growth factor fusion protein s showed small but significant uptake into the brain parenchyma.