BIOTECHNOLOGY
A DEVELOPMENT OF A
ntibodies are Y-shaped protective proteins produced by B lymphocytes in response to invading pathogens. When
B lymphocytes are exposed to foreign antigens expressed by antigen-presenting cells such as dendritic cells or macrophages, they become differentiated and activated by antigen-coated pathogens or T helper cells. Mature B lymphocytes secrete antigen- specific antibodies or differentiate them into memory B lymphocytes for long- term protection (Fig. 1). B lymphocytes can recognise antigens, and each B lymphocyte can only bind to a single type of antigen, indicating its specificity. Tis specific feature shows the potential role of antibodies in therapeutic reagents as modern medicine.
BACKGROUND Te prophylactic and protective abilities of antibodies were first discovered in the late 19th century, where passive transmission of antibodies from infected animals provided immunity against diphtheria. Antibodies provide defence against transmitted diseases and are capable of eliminating the infection.
Polyclonal antibodies contain a number
of diverse antibodies that recognise different antigens. However, because of limited supply, batch-to-batch variation, cross- reactivity, and lack of specificity, the use of polyclonal antibodies is limited. On the contrary, monoclonal antibodies (mAbs) exhibit specificity to a single epitope. In 1975, Köhler and Milstein produced the first mAb via hybridoma technology, which uses the fusion of antibody-producing cells isolated from the spleen tissue of animals immunised with immortal myeloma cells (Fig. 2). Tus, the ‘hybridoma’ was born with its promise of producing unlimited quantities of monospecific antibodies, greatly advancing the basic research and potential for their clinical use. Although mAbs demonstrate a
promising therapeutic index, the murine protein limits their therapeutic application in humans due to allotypic immune responses that clear the non-human antibody rapidly. In recent years, advances in genetic engineering technology have moved antibody production to a new era of humanised antibody production that is suitable for the therapy of humans. In humanised antibody production, human immunoglobulin loci are
NTIBODY PRODUCTION From bench to bedside: antibodies revolutionise treatment, explains Emma Zhao
introduced into the germline of transgenic mice to produce human antibodies to solve immune rejection. Te major drawbacks of mAbs are that they are expensive and time-consuming to prepare. More importantly, humanised mouse models lack critical molecules for robust functional cellular and humoral responses. Another humanised antibody approach is via complementarity-determining region (CDR) grafting, which was developed by Gregory P. Winter in 1986. In this approach, non-human antibody CDR sequences are transplanted into the human framework sequence, allowing mAbs to maintain binding specificity to the target antigen. Humanised antibodies have yielded promising results for the treatment of diseases that need long-term treatment, such as cancer and infectious diseases. Additionally, phage display and single B cell technologies have been developed to produce mAbs. Phage display is used for in vitro mAb selection and the rapid identification of peptides or antibody fragments. In 1985, George P. Smith used recombinant DNA technology to fuse foreign peptides with M13 bacterio phage to display the foreign peptide on the phage
Fig. 1. The process of antibody production 40
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