Antibodies for Therapeutic Uses and the Evolution of Biotechniques

Abstract

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.

A human scFv antibody generation pipeline for proteome research

“…To date, antibodies represent the fastest growing class of biological therapeutics on the market and are indispensable as detection reagents in research and diagnostics (Dübel, 2007;Hagemeyer et al, 2009;Nieri et al, 2009). For proteome research, antibodies or alternative scaffolds are a key tool for the decryption of the human proteome (Aebersold and Mann, 2003;Berglund et al, 2008;Dübel et al, 2010;Hust and Dübel, 2004;Ohara et al, 2006;Skerra, 2007;Taussig et al, 2007;Wingren et al, 2009).…”

Microneedle-Based Intradermal Delivery Enables Rapid Lymphatic Uptake and Distribution of Protein Drugs

“…The development and use of peptide and protein therapeutic drugs is increasing, and their administration continues to rely on standard parenteral injection techniques (1)(2)(3). Alternative delivery methods, such as transdermal delivery, are typically limited by diffusion through the stratum corneum of the skin (4).…”

Selection of a human butyrylcholinesterase-like antibody single-chain variable fragment resistant to AChE inhibitors from a phage library expressed inE. coli

“…This strategy was largely successful and has been used to obtain many antibodies accelerating a large number of reactions. 32 In spite of this success, the catalytic efficiency of the elicited abzymes was generally poor, their accelerating properties being about 10,000 times less than that observed for natural enzymes. An abzyme selection based on the investigation of the binding activity against transition state analogs of the natural substrate, even if successful, might lead to an artificial enzyme with reaction mechanism, active site geometry and sensitivity to inhibitors, very close to those of the natural enzyme.…”