Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study — in particular, transgenic mice and yeast or phage display — renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.
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The authors declare no competing financial interests.
Antibody allotypes are defined by their polymorphism within the immunoglobulin heavy and light chains. Natural allelic genetic variation in the constant region of genes in humans may predispose a given patient to anti-drug antibody responses if the drug is a foreign allotype.
- Ankylosing spondylitis
A chronic condition of unknown aetiology that is characterized by inflammation of the joints of the spine and pelvis. Disease progression may result in fusion of the joints.
- Anti-idiotypic antibody
An antibody that targets the hypervariable antigen-binding domain of an exogenous immunoglobulin, including therapeutic monoclonal antibodies. As the constant regions are fairly conserved, with the exception of allotypic differences, many anti-immunoglobulin responses will be directed against the highly variable, antigen-binding domain.
- Cryopyrin-associated periodic syndromes
(CAPS). A group of rare, inherited autoimmune disorders associated with over-secretion of interleukin-1 that may cause inflammation of the skin, eyes, bones, joints and meninges.
- Phage-display technologies
A method involving the use of bacteriophages to select desirable antibody variable domains based on their binding properties.
- Pre-transplant desensitization
In the recipient patient, reduction of antibody-producing cells or the amount of circulating antibodies that might target foreign tissue prior to transplantation of an organ.
- Systemic lupus erythematosus
A chronic, inflammatory autoimmune disease affecting connective tissue throughout the body.
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Nelson, A., Dhimolea, E. & Reichert, J. Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 9, 767–774 (2010). https://doi.org/10.1038/nrd3229
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