BIOTECHNOLOGY - Inshyna N.M. - 2009

CHAPTER 4. MEDICAL BIOTECHNOLOGY

Immunobiotechnology. Technology for Producing Monoclonal Antibodies

In 1975, the journal Nature published a paper by G. Köhler describing a novel method for producing immune Proteins (Monoclonal Antibodies) based on hybrid Cells known as hybridomas. Hybridomas were obtained by fusing a lymphocyte with a Bone Marrow tumor Cell (myeloma). Hybridomas combine The properties of both parent cells: the capacity for unlimited division and the synthesis of antibodies. Antibodies synthesized by cloned hybridomas were named monoclonal antibodies. They are IMMUNOGLOBULINS identical in Structure and Specificity.

In 1984, Köhler, Milstein, and Jerne were awarded the Nobel Prize in Physiology or Medicine for The Development of monoclonal antibody technology.

The production of monoclonal antibodies occupies a leading position in biotechnology. Previously, the only source of antibodies was the Blood serum of immunized animals. Serum antibodies do not represent a single homogeneous preparation, as other antibodies are invariably present in the blood in certain amounts.

Monoclonal antibodies exhibit high specificity; they recognize not only individual protein molecules but also Amino Acid Substitutions within their structure. Using monoclonal antibodies, it has been established that the substitution of a single amino acid can lead to the appearance of an oncogenic protein.

Monoclonal antibodies are used to obtain high-purity preparations of BIOLOGICALLY ACTIVE SUBSTANCES. They serve as an essential tool for enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay of Antigens of any origin. Biosensors based on monoclonal antibodies are successfully employed in environmental monitoring, biotechnological processes, and the Analysis of the internal environment of humans and animals.

Monoclonal antibodies are utilized for detecting various compounds and diagnosing infectious diseases:

- Hormones (human chorionic gonadotropin, Growth Hormone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, thyroxine);

- tumor markers (carcinoembryonic antigen, interleukin-2 receptor, epidermal growth factor receptor);

- cytokines (interleukins 1-8, colony-stimulating factor);

- Pharmaceuticals (theophylline, gentamicin, cyclosporine);

- infectious diseases (chlamydia, herpes, rubella, hepatitis B, AIDS).

Potential medical Applications OF MONOCLONAL antibodies are summarized in Table 4.3.

Class="center">Table 4.3

Application of Monoclonal Antibodies in Medicine

Monoclonal antibodies are synthesized by hybridomas—hybrid cells formed by the fusion of human lymphocytes with mouse myeloma cells. It is estimated that 1 g of monoclonal antibodies can be obtained from 50 to 100 mice. When monoclonal antibodies are used as therapeutic agents, side effects associated with the initiation of inflammatory processes may occur. This necessitates the development of human monoclonal antibodies.

The Production of Human monoclonal antibodies via traditional hybridoma technology presents certain difficulties:

- Human Chromosomes are unstable in hybrid cells generated by fusing human lymphocytes with mouse myeloma cells;

- researchers have been unable to obtain effective human myeloma cell lines capable of replacing mouse myeloma cells;

- human immunization with various antigens is restricted by ethical standards.

Thus, obtaining human monoclonal antibodies requires alternative approaches. For instance, human immune stem cells are introduced into mice with severe combined immunodeficiency (SCID mice). In response to antigen administration, these mice produce human antibodies.

Attempts have also been made to introduce human immunoglobulin genes into mouse embryos to create Transgenic Mice capable of producing human antibodies upon immunization. Both of these Methods are quite labor-intensive, prompting scientists to develop Introduction/32.html">Genetic Engineering techniques for antibody production.