Recombinant antibodies: a novel approach to cancer diagnosis and therapy

Abstract

Recombinant antibodies and their fragments currently represent over 30% of all biological proteins undergoing clinical trials for diagnosis and therapy. These reagents dominate the cancer-targeting field, as highlighted by the recent approval of the first engineered therapeutic antibodies by the Food and Drugs Administration (FDA). Last year, important advances have been made in the design, selection and production of recombinant antibodies. The natural immune repertoire and somatic cell affinity maturation has been superseded by large antibody display libraries and rapid molecular evolution strategies. These novel libraries and selection methods have enabled the rapid isolation of high-affinity cancer targeting and antiviral antibodies, the latter capable of redirecting viruses for gene therapy applications. In alternative strategies for cancer diagnosis and therapy, recombinant antibody fragments have been fused to radioisotopes, drugs, toxins, enzymes and biosensor surfaces. Antibody-directed cancer pre-targeting followed by prodrug activation (ADEPT) has proved a most promising therapeutic strategy. Multi-specific antibodies have been effective for cytotoxic T-cell recruitment and antibody-fusion proteins have delivered enhanced immunotherapeutic and vaccination strategies. The new millennium is indeed an exciting time for the design, selection and formulation of a range of new antibody-based products for cancer diagnosis and therapy.