Shark novel antigen receptors--the next generation of biologic therapeutics?
Over recent decades we have witnessed a revolution in health care as new classes of therapeutics based on natural biological molecules have become available to medical practitioners. These promised to target some of the most serious conditions that had previously evaded traditional small molecule drugs, such as cancers and to alleviate many of the concerns of patients and doctors alike regarding adverse side effects and impaired quality of life that are often associated with chemo-therapeutics. Many early 'biologics' were based on antibodies, Nature's answer to invading pathogens and malignancies, derived from rodents and in many ways failed to live up to expectations. Most of these issues were subsequently negated by technological advances that saw the introduction of human or "humanized' antibodies and have resulted in a number of commercial 'block-busters'. Today, most of the large pharmaceutical companies have product pipelines that include an increasing proportion of biologic as opposed to small molecule compounds. The limitations of antibodies or other large protein drugs are now being realized however and ever more inventive solutions are being sought to develop equally efficacious but smaller, more soluble, more stable and less costly alternatives to broaden the range of drug-able targets and therapeutic options. The aim of this chapter is to introduce the reader to one such novel approach that seeks to exploit a unique antibody-like protein evolved by ancestral sharks over 450 M years ago and that may lead to a host of new therapeutic opportunities and help us to tackle some of the pressing clinical demands of the 21 st century.
Barelle
Caroline
C
Wyeth Research, Cornhill Road, Foresterhill, Aberdeen, AB25 2ZS, Scotland, UK.
Gill
Davinder S
DS
Charlton
Keith
K
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000941:Antigens / Q000737:chemistry*; D001688:Biological Products; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004220:Disulfides / Q000737:chemistry; D004284:Dogfish; D015195:Drug Design; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012754:Sharks / Q000276:immunology* / Q000502:physiology; D013678:Technology, Pharmaceutical / Q000379:methods
D000906:Antibodies; D000941:Antigens; D001688:Biological Products; D004220:Disulfides; D007136:Immunoglobulins