Historical development of monoclonal antibody therapeutics.
Since the first publication by Kohler and Milstein on the production of mouse monoclonal antibodies (mAbs) by hybridoma technology, mAbs have had a profound impact on medicine by providing an almost limitless source of therapeutic and diagnostic reagents. Therapeutic use of mAbs has become a major part of treatments in various diseases including transplantation, oncology, autoimmune, cardiovascular, and infectious diseases. The limitation of murine mAbs due to immunogenicity was overcome by replacement of the murine sequences with their human counterpart leading to the development of chimeric, humanized, and human therapeutic antibodies. Remarkable progress has also been made following the development of the display technologies, enabling of engineering antibodies with modified properties such as molecular size, affinity, specificity, and valency. Moreover, antibody engineering technologies are constantly advancing to enable further tuning of the effector function and serum half life. Optimal delivery to the target tissue still remains to be addressed to avoid unwanted side effects as a result of systemic treatment while achieving meaningful therapeutic effect.
Nissim
A
A
Bone and Joint Research Unit, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, University of London, Charterhouse Square, London, UK. a.nissim@qmul.ac.uk
Chernajovsky
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000266:history* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000915:Antibody Affinity; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007167:Immunotherapy / Q000266:history* / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D019151:Peptide Library; D011487:Protein Conformation; D015202:Protein Engineering / Q000266:history; D011993:Recombinant Fusion Proteins / Q000266:history
D000911:Antibodies, Monoclonal; D019151:Peptide Library; D011993:Recombinant Fusion Proteins