Recombinant antibody

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A recombinant antibody is an antibody - a protein with immunological activity - that is produced by genetic engineering . Antibody production takes place by cloning in expression vectors and transformation in host cells. Escherichia coli , yeasts and plants are currently in use as host cells . In contrast to the production of monoclonal and polyclonal antibodies , no immunization is necessary to obtain recombinant antibodies . There is no use of laboratory animals .

Recombinant antibodies are playing an increasingly important role in diagnostics and therapy . They have become particularly indispensable for the manufacture of proteinogenic therapeutics.

Production of recombinant antibodies

The classic way of producing antibodies is to immunize vertebrates ( domestic goats , domestic pigs , rabbits, etc.) with an antigen . The antigen can be almost any macromolecule or a hapten (small molecule coupled to a carrier protein). In general, polyclonal antibodies are obtained here.

The development of hybridoma technology allows the production of monoclonal antibodies. This also results in a first method for obtaining recombinant antibody fragments. The mRNA can be isolated from hybridoma cells using recombinant DNA and RNA techniques. A cDNA synthesis and an amplification and cloning of the nucleotide sequence coding for the antibody can then take place. Since certain disadvantages occur with the classic methods of antibody production, attempts were made at a very early stage to breed recombinant antibodies in bacteria . However, the focus here was exclusively on antibody fragments that contained the specific antigen binding site. It was not until 1988 that the first AK fragments could be functionally produced in E. coli . This was achieved by secretion of the antibody chains into the periplasmic space of the cell with the help of N-terminal signal sequences. This is where the disulfide bond formation necessary for protein folding takes place.

E. coli is still the most widely used production system for recombinant antibodies worldwide. The phage display technique offers an alternative to the time-consuming and costly hybridoma technique . It works completely without immunization and thus without the use of laboratory animals. It is suitable for the selection of highly specific recombinant AK fragments and the identification of the epitope in vitro, i.e. outside the living organism. In addition to the use of prokaryotes to produce recombinant antibodies, intensive research is being carried out on other production systems. Possibilities of making plants usable as such are currently being investigated in particular.

Therapeutic Recombinant Antibodies

The attempts to use recombinant antibodies for therapeutic purposes were initially only partially successful. Often they were identified and attacked by the organism as antigens. This problem has now been resolved in many fields of application by making it possible to adapt the antibody fragments to the organism ( humanizing ). The term antibody engineering has also been established here, which suggests that the adaptation of recombinant antibodies to the desired properties is now more of an engineering approach than a classical biological one. Terms such as affinity maturation, humanization, the design of fusion proteins, and increasing production yields are discussed. Recombinant antibodies are very promising and are used in more and more areas of medicine. There is already a wide range of recombinant antibodies approved worldwide and also in Germany. The website of the researching pharmaceutical companies in Germany provides an overview of this . The range of applications of approved recombinant antibodies now extends from the diagnosis and / or therapy of various types of cancer to the treatment of multiple sclerosis , asthma and Alzheimer's disease . Intensive research is being carried out in particular on the treatment of the latter with a view to the use of recombinant antibodies.

further reading

Individual evidence

  1. ↑ U. Bornscheuer: Lecture Biotechnology II. ( Memento from February 17, 2007 in the Internet Archive ), Institute for Chemistry and Biochemistry, University of Greifswald.
  2. ↑ S. Dübel and A. Schmiedl: Recombinant Antibodies and Phage Display. ( Memento from January 31, 2012 in the Internet Archive ) Institute for Biochemistry and Biotechnology, Technical University of Braunschweig
  3. ↑ a b S. Schleker: Production and characterization of recombinant antibodies and scFv fusion proteins for the generation of Phytophthora infestans - resistant potato plants. (PDF; 2.1 MB) Dissertation, RWTH Aachen, 2009, DNB 997138998 .
  4. ↑ a b S. Lange: Establishment of new methods for the production of recombinant antibodies and for the specific selection of antibody variants in high throughput. Institute for Technical Biochemistry, Dissertation, University of Stuttgart, 2002, DNB 965274241 .
  5. ↑ BOKU, Institute for Molecular Plant Physiology; (On-line)
  6. ↑ S. Dübel: ( Page no longer available , search in web archives: Recombinant Antibodies - Discover the possibilities. ) In: Laborjournal 6, 2005@1@ 2Template: Toter Link / www.bbt.tu-bs.de
  7. ↑ Heidelberg University Hospital, National Center for Tumor Diseases (NCT): Recombinant therapeutic antibodies.
  8. ↑ vfa, The research-based pharmaceutical company: Approved genetic engineering drugs in Germany.
  9. ↑ antibodies online; Alzheimer's: Recombinant antibody used to treat Alzheimer's.