Recombinant antibodies for cancer diagnosis and therapy

Abstract

Recombinant antibodies now represent over 30% of biopharmaceuticals in clinical trials, highlighted by the recent approvals for cancer immunotherapy from the FDA which has awoken the biotechnology industry. Sales of these antibodies are increasing very rapidly to a predicted US$ 3 billion per annum worldwide by 2002. Since the development of new therapeutic reagent into commercial product takes 10 years, the recent FDA-approved antibodies are based on early antibody designs which are now considered primitive. Emerging technologies have created a vast range of novel, recombinant, antibody-based reagents which specifically target clinical biomarkers of disease. In the past year, radiolabelling of antibodies has increased their potential for cancer imaging and targeting. Recombinant antibodies have also been reduced in size and rebuilt into multivalent molecules for higher affinity. In addition, antibodies have been fused with many molecules including toxins, enzymes and viruses for prodrug therapy, cancer treatment and gene delivery. Recombinant antibody technology has enabled clever manipulations in the construction of complex antibody library repertoires for the selection of high-affinity reagents against refractory targets. Although phage display remains the most extensively used method, this year high affinity reagents have been isolated using alternative display and selection systems such as ribosome display and yeast display confirming the emergence of new display methods. Furthermore, innovative affinity maturation strategies have been developed to obtain high affinity reagents. This review focuses on developments in the last 12 months and describes the latest developments in the design, production and clinical use of recombinant antibodies for cancer diagnosis and therapy.