Health, Biotech
GenScript ProBio
GenScript ProBio
The process of developing and discovering humanization antibodies can be described as the procedure of finding new therapeutic antibodies that fight various illnesses like cancer, HIV, autoimmune, hereditary, and many more. The number of fully human monoclonal antibodies that have received approval for clinical use has rapidly increased following when Humira(r) was approved Humira(r) at the end of 2002. Since the time, more than 30 monoclonal antibodies and a bispecific fragment of an antibody have been approved to treat many different ailments. As the need for these drugs increases and so is the need to improve the effectiveness of existing fully human monoclonal antibody detection techniques. What are the strengths and drawbacks of the current methods? What are the ways these approaches will evolve over the coming years? Early Approaches to Fully Human Monoclonal Antibody Discovery
First antibodies are created by mice. Inspiring by the groundbreaking creation of hybridoma technologies, researchers quickly discovered a method to generate sufficient amounts of these biomolecules for testing their therapeutic efficacy. But, along with the realization of the therapeutic value for these antibodies, was the realization that xenogeneic molecules cause immunogenic reactions in patients. These reactions came to be known as "the human anti-mouse antibodies (HAMA) immune response. It was the discovery of HAMA response has prompted the further creation of methods to reduce the immunogenicity of xenogeneic antibodies (i.e. humanization). Furthermore, rapid technological advancement has allowed for the creation of monoclonal antibodies that are fully human. These fully human proteins are frequently discovered through phage display as well as hybridoma formation using transgenic mice. Since the release of the first human monoclonal antibody Humira(r) in 2002, the first monoclonal antibody that was fully Humira(r) at the end of 2002 via the display of phages of antibodies from human beings, the amount of fully human monoclonal antibodies that have been approved for therapeutic use continues to increase, every year. As of December 31, 2020, there are 30 monoclonal human antibodies and one completely human bispecific antibody (Lumoxiti(r)) are cleared for use in clinical settings. Of the 30 mAbs, 8 were created by screening human antibody libraries that are complex with phage display technology and the remaining 22 mAbs came from transgenic mouse development. Advantages and Limitations of Fully Human Monoclonal Antibody Generation Technologies While the majority of fully human monoclonal antibodies are produced by transgenic mice, the established techniques for this technique have some limitations. In particular, while transgenics may produce highly specific and affinity-matured antibodies, they have limitations regarding antigenicity and the normal defenses of the human host. This is why toxic antigens can't be used to immunize mice, and beneficial antigens or targets may not trigger an appropriate immune response in the host. In contrast, Phage display technologies offer enormous potential for scalability and parallelization, as well as miniaturization. However, these methods do not preserve the information about pairing between heavy and light chains, resulting in a non-natural pairing of antibodies, which can result in lower affinity. Furthermore, the majority of antibodies created through phage display could require an additional process of affinity maturation in vitro which are normally carried out by immunized transgenic mice. The amount of therapeutic antibodies produced by transgenics is steadily growing. The experts disagree on the factors for this increase because transgenics and phage display-derived antibodies possess similar clinical efficacy. In addition to the reasons for the popularity of each method, Both technologies have plenty of scopes to improve. Transgenics, for instance, will benefit from the upcoming change from the low yield hybridoma method to the high-throughput, higher yield B cell cloning technique. Additionally, the display of antibodies is likely to focus on mammalian and yeast display systems to address the issues of expressing antibodies in the bacterial system. Furthermore, the technology could be more effective by connecting the display systems of the past together with FACS sorting analysis as well as next-generation sequencing. CONCLUDING REMARKS There is no doubt that there is a growing demand for human monoclonal antibodies for therapeutic purposes. Recently two techniques have dominated the development of these sought-after biopharmaceuticals - phage display and the generation of antibodies in transgenic mice. Even though the latter has seen an increasing amount of attention Both technologies are likely to play a significant role in the near future of human-specific monoclonal antibody discovery. Furthermore, with the introduction of single-cell technology as well as Next-Generation Sequencing, both methods will likely rapidly evolve to overcome their limitations. Read also: single domain antibody
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AuthorGenScript ProBio is the bio-pharmaceutical CDMO segment of the world's leading biotech company GenScript Biotech Corporation (Stock Code: 1548.HK). Founded in 2002 in New Jersey, ArchivesNo Archives Categories |