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Functional properties of antibody insulin-like growth factor fusion proteins
Genetic engineering and expression techniques have been used to produce 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 CH1, immediately after the hinge, and at the end of CH3. Fusion heavy chains of the expected molecular weight were expressed, assembled with a co-expressed light chain, and secreted. The resulting molecules continued to bind antigen; they also bound the growth factor receptors, albeit with decreased affinity. The molecule with IGF1 attached after CH3 (CH3-IGF1) had reduced ability to carry out complement-mediated cytolysis. In contrast the molecule with IGF2 attached after CH3 (CH3-IGF2) showed an approximately 50-fold increase in its ability to effect complement-mediated cytolysis and so should be an effective cytolytic agent. Both CH3-IGF1 and CH3-IGF2 bound Fc gamma RI with affinity similar to that of IgG3. The growth factor fusion proteins showed small but significant uptake into the brain parenchyma.
Genetic engineering and expression techniques have been used to produce 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 CH1, immediately after the hinge, and at the end of CH3. Fusion heavy chains of the expected molecular weight were expressed, assembled with a co-expressed light chain, and secreted. The resulting molecules continued to bind antigen; they also bound the growth factor receptors, albeit with decreased affinity. The molecule with IGF1 attached after CH3 (CH3-IGF1) had reduced ability to carry out complement-mediated cytolysis. In contrast the molecule with IGF2 attached after CH3 (CH3-IGF2) showed an approximately 50-fold increase in its ability to effect complement-mediated cytolysis and so should be an effective cytolytic agent. Both CH3-IGF1 and CH3-IGF2 bound Fc gamma RI with affinity similar to that of IgG3. The growth factor fusion proteins showed small but significant uptake into the brain parenchyma.