Phage display--a powerful technique for immunotherapy: 1. Introduction and potential of therapeutic applications

Abstract

One of the most effective molecular diversity techniques is phage display. This technology is based on a direct linkage between phage phenotype and its encapsulated genotype, which leads to presentation of molecule libraries on the phage surface. Phage display is utilized in studying protein-ligand interactions, receptor binding sites and in improving or modifying the affinity of proteins for their binding partners. Generating monoclonal antibodies and improving their affinity, cloning antibodies from unstable hybridoma cells and identifying epitopes, mimotopes and functional or accessible sites from antigens are also important advantages of this technology. Techniques originating from phage display have been applied to transfusion medicine, neurological disorders, mapping vascular addresses and tissue homing of peptides. Phages have been applicable to immunization therapies, which may lead to development of new tools used for treating autoimmune and cancer diseases. This review describes the phage display technology and presents the recent advancements in therapeutic applications of phage display.

Keywords: antibody libraries; autoimmune diseases; immune-diagnostics; neurological disorders; phage display; transfusion medicine; tumor targeting.

Figure 1. Schematic presentation of phage display systems. The black circle represents molecule displayed on various phage proteins (listed below the scheme). The rectangle inside the phage represents nucleic acid.

Figure 2. Schematic presentation of antibody fragments. Fab (the antigen-binding fragment), scFab (the single chain antigen-binding fragment), scFabΔC (the scFab variant without cysteins), scFv (the single chain fragment variable), Fv (the fragment variable), VHdAb (the antibody with one variable heavy chain domain), CRAb (the construct specific to adjacent epitopes on the antigen).

Figure 3. Schematic presentation of biopanning. Phage display library is incubated with target molecule immobilized on solid support. Specific library phage is bound to molecule and unbound phages are washed out. The specific phages are eluted and amplified in bacteria. After several rounds, amplified phages could be analyzed and amplified to obtain diagnostic and therapeutic agents.