Antibodies for therapeutic uses and the evolution of biotechniques

Protein therapeutics are playing an expanding role in modern medicinal chemistry. Among them, native or engineered molecules exploiting the binding and catalytic potential of the immune repertoire form an extremely exciting and emerging business area. They represent by far the single largest category of biopharmaceutical substances under investigation. The fast increase of this pharmaceutical category paralleled the scientific and technical progress from murine to chimeric, humanized and, finally, human engineered antibodies. Indeed, the development of the phage display technology, allowing libraries of shuffled murine or human antibody binding domains to be screened for affinity against a selected target antigen or activity against a specific reaction substrate, open new perspectives, disclosing the opportunity to circumvent restrictions inherent to the in vivo immunisation. Transgenic technology represents another powerful method for generating fully human monoclonal antibodies against a wide variety of drug targets, while recombinant technology continues to evolve, improving the pharmacodynamic and pharmacokinetic properties of antibody therapeutics, with the production of different antibody constructs or formats, such as bispecific antibodies, diabodies and others, and different functional activities, such as catalysis, cellular internalisation and antigen-mimicking. The aim of the present review is to overview native or recombinant antibodies while discussing the underlying antibody technology, with the aim to favour understanding of the antibody therapeutics that are in use or will enter market in the near future.