PHAGE DISPLAY AS A RAPID GENE-EXPRESSION SYSTEM - PRODUCTION OF BIOACTIVE CYTOKINE-PHAGE AND GENERATION OF NEUTRALIZING MONOCLONAL-ANTIBODIES

Proteins, such as hormones, enzymes, or antibody binding sites, can be expressed in an active conformation on the surface of filamentous bac teriophage. Although the phage display technology was originally devel oped for binding studies, we demonstrate here that this technique can rapidly provide cytokines for studies of biological activity and for r aising neutralizing monoclonal antibodies. A phage M13-based cloning v ector was constructed that facilitated the expression of human interle ukin 3 (hIL-3) on the phage surface. The recombinant phage could stimu late the growth of the hIL-3 dependent cell line M-07, providing evide nce for the display of hIL-3 in an active form. Injection of recombina nt phage into mice provoked an immune response to hIL-3, and neutraliz ing monoclonal antibodies directed against native hIL-3 could be estab lished from these mice with a high frequency.