MAKING ANTIBODIES BY PHAGE DISPLAY TECHNOLOGY

Antibody fragments of predetermined binding specificity have recently been constructed from repertoires of antibody V genes, bypassing hybri doma technology and even immunization. The V gene repertoires are harv ested from populations of lymphocytes, or assembled in vitro, and clon ed for display of associated heavy and light chain variable domains on the surface of filamentous bacteriophage. Rare phage are selected fro m the repertoire by binding to antigen; soluble antibody fragments are expressed from infected bacteria; and the affinity of binding of sele cted antibodies is improved by mutation. The process mimics immune sel ection, and antibodies with many different binding specificities have been isolated from the same phage repertoire. Thus human antibody frag ments have been isolated with specificities against both foreign and s elf antigens, including haptens, carbohydrates, secreted and cell surf ace proteins, viral coat proteins, and intracellular antigens from the lumen of the endoplasmic reticulum and the nucleus. Such antibodies h ave potential as reagents for research and in therapy.