Recombinant antibodies for cancer diagnosis and therapy

Recombinant antibodies currently represent over 30% of biopharmaceuticals in clinical trials, highlighted by the recent Food and Drug Administration (FDA) approvals of Zevalin(TM) (ibritumomab-tiuxetan; IDEC Pharmaceuticals, San Dieago, CA, USA) for cancer radioimmunotherapy and Humira(TM) (adalimumab; Abbott Laboratories, IL, USA) for rheumatoid arthritis. Together, these FDA approvals have excited the biotechnology industry, particularly since sales of recombinant antibodies are increasing rapidly to a predicted US dollar 4 billion per annum worldwide in 2003. To date, 10 engineered therapeutic antibodies have gained FDA approval and many others are in Phase III trials. Many recent FDA-approved antibodies are simple molecular designs that have taken 10 years to be developed into effective therapeutic reagents. Emerging new technologies have created a vast range of recombinant, antibody-based reagents, which specifically target clinical biomarkers of disease. 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, drugs and viruses, for prodrug therapy, cancer treatment and gene delivery. Recombinant antibody technology has enabled clever manipulations in the construction of complex in vitro libraries for the selection of high-affinity reagents against refractory targets. Furthermore, innovative affinity maturation methods have been developed which enable rapid selection of extremely 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.