Monoclonal antibody

Monoclonal antibodies are antibodies, ie immunologically active proteins produced by a cell line ( clone ) are produced which go back to a single B- lymphocytes, and are directed against a single epitope. A physiologically (naturally) occurring immune response against an antigen that has penetrated into the body, however, is always polyclonal and directed for example against many different epitopes on a bacterium.

In the diagnostics and research, monoclonal antibodies play a major role, since they can bind a number of molecules with high specificity. The binding of the antibodies can then be detected with different techniques. This antigen -antibody reaction is the basis for many diagnostic procedures (e.g., immunophenotyping, FACS, immunohistochemistry, ELISA, ELISPOT, radioimmunoassay, and Western blot).

Many of the monoclonal antibodies recognized cell surface antigens of human cells are classified into CD nomenclature.

Production of monoclonal antibodies

The principle of the production of monoclonal antibodies was published in 1975 by César Milstein, Georges Köhler and Niels Jerne, which in 1984 received the Nobel Prize for Medicine. The technique is based on the fusion of antibody-producing B cells with cells of a myeloma cell line, thereby resulting in hybrid cells that produce antibodies of a particular specificity unlimited ( hybridoma technology).

In the production of monoclonal antibodies against a particular antigen, a mouse with this antigen is first infected (1, see Figure ). Due to the immune response leads to the formation of B- lymphocytes produce antibodies that react with the antigen and which accumulate in the spleen. Removed from the spleen (2) the B- lymphocytes are isolated and cells ( plasma cells) of a myeloma ( plasmocytoma ) derived cell line ( 3) is fused (4), there occur so-called hybridoma cell lines (5). These hybridoma cells combine properties of their cells of origin: B- lymphocyte the property to produce a specific antibody from the myeloma cell's ability to unlimited growth in the test tube. For the production of the monoclonal antibody, the hybridoma cell line is selected that best suits the desired epitope on the antigen binding (6). The immortal cell line will be saved, and the cell supernatant is harvested periodically when required. Production of monoclonal antibodies can be performed in vitro ( 7 ), or in vivo (7b). The antibodies (8 ) are called monoclonal because they derive from a single origin -B - cell and therefore all are identical.

The hybrid cells are selected by means of a so-called HAT medium. In this medium are hypoxanthine ( a naturally occurring purine derivative ), thymidine and aminopterin (cell poison which inhibits the biosynthesis of purine and pyrimidine bases ) included. B lymphocytes, and thus the hybrid cells can metabolize hypoxanthine, and thymidine, thus blocking that is caused by the handle aminopterin. The myeloma cells used are relative to the alternative pathway deficient mutants and die in the HAT medium. The unfused B lymphocytes have a limited lifetime, making it easy to find only the hybrid cells in culture after several passages.

A major advance in particular for cloning human antibody is the technique of phage display.

Therapeutic monoclonal antibodies

The attempts to use monoclonal antibodies in therapy were initially not very successful. The antibodies used mouse (murine antibody ending: - OMAB ) act in the human organism itself as an antigen and can trigger an immune response against them. Also important for their desired effect interaction with cells of the immune system of the recipient was not optimal due to the different species.

Significant progress has been made ​​only after it has been possible in recent years to develop modified human antibodies better adapted monoclonal antibodies.

In addition, also antibody conjugates, such as immunocytokines, for therapeutic and diagnostic applications, particularly, used in cancer immunotherapy.

Terminology of monoclonal antibodies

The free trade names of therapeutic monoclonal antibodies with the suffix " mab ... ", which stands for " monoclonal antibody ". After similarity to the human antibodies, a distinction ( in ascending order):

• Murine antibodies (of the mouse): suffix- OMAB
• Antibodies of the primates: ending- Imab
• Chimeric antibodies: ending- ximab (Only the variable part of the AK is mouse protein )
• Humanized antibodies: suffix- zumab (Only the antigen binding sites are mouse protein )
• Human antibodies: ending- umab

Lists developed antibodies

Approved or in clinical trials (Phase III) located therapeutic monoclonal antibodies

1in Germany has not approved (possibly out of date! ) 2in clinical examination Approved 3Trotz potential rare serious side effects from the FDA under strict conditions back in the U.S., European approval since 6/2006 4Entwicklung set. 5Durch the manufacturer - as MabCampath ® - removed from the market to the substance - to bring under a new trade name and another indication (MS ) back on the market. Criticized by the Drug Commission of the German Medical Association ( AkdÄ ).

Approved for the in vivo diagnosis monoclonal antibodies

Withdrawn or abandoned diagnostic monoclonal antibodies

Located in preclinical testing or Phase I / II trials therapeutic monoclonal antibodies

Withdrawn or abandoned therapeutic monoclonal antibodies

Swell

• Cancer immunotherapy
• The diagnostic method in hematology and oncology
• Biotechnology
• Antibody