Abstract
Monoclonal antibodies (mAbs) have become one of the most important classes of biopharmaceutical products, and they continue to dominate the universe of biopharmaceutical markets in terms of approval and sales. They are the most profitable single product class, where they represent six of the top ten selling drugs. At the beginning of the 1990s, an in vitro antibody selection technology known as antibody phage display was developed by John McCafferty and Sir. Gregory Winter that enabled the discovery of human antibodies for diverse applications, particularly antibody-based drugs. They created combinatorial antibody libraries on filamentous phage to be utilized for generating antigen specific antibodies in a matter of weeks. Since then, more than 70 phage–derived antibodies entered clinical studies and 14 of them have been approved. These antibodies are indicated for cancer, and non-cancer medical conditions, such as inflammatory, optical, infectious, or immunological diseases. This review will illustrate the utility of phage display as a powerful platform for therapeutic antibodies discovery and describe in detail all the approved mAbs derived from phage display.
Highlights
Specialty section: This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology
The findings from this study have demonstrated the efficacy of lanadelumab in preventing hereditary angioedema (HAE) attacks, leading to its approval by the US FDA in 2018 for the treatment of patients with type I or II HAE
Antibody phage display is a versatile, reproducible, and functional technology that can be utilized to isolate antibody candidates for numerous disease indications. While it is the most common and well-established form of display technologies, the success of isolating useful antibodies is highly dependent on the quality and the nature of the targeted antigen used in biopanning and the size and quality of the library
Summary
They have a high success rate in clinical development; for instance, it has been reported that the probability of FDA approval for mAbs in phase I of development is ∼14.1%, which is almost twice the approval rate of small molecule drugs (∼7.6%) [10, 11]. Such factors make biopharmaceutical companies more motivated and willing to sponsor the development of these pharmaceutical products. Allison and Tasuku Honjo were honored by the 2018 Nobel Prize in Physiology or Medicine for their discoveries of cancer immunotherapy via the use of antibody blockade of the T-cell inhibitory receptor (CTLA-4) and programmed cell death protein 1 (PD1) to enhance anti-tumor immune responses [17, 18]
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