Zusammenfassung.
In den letzten beiden Jahrzehnten wurde eine Vielzahl gentechnisch hergestellter Arzneimittel
zur medizinischen Behandlung zugelassen. Solche Medikamente zeichnen sich durch große
Wirksamkeit und optimale Arzneimittelsicherheit aus. Es handelt sich dabei um Hormone,
Enzyme, Wachstums- und Gerinnungsfaktoren, Antikörper sowie Impfstoffe. Diese Proteine
werden mithilfe der DNA-Rekombinationstechnik hergestellt. Das für das Protein codierende
Gen wird mittels eines Plasmids in einen Mikroorganismus oder eine Zelllinie eingeführt,
in denen die Geninformation in ein Protein übersetzt wird. Für die industrielle Herstellung
des rekombinanten Medikamentes werden biotechnische Verfahren eingesetzt. Die gentechnisch
veränderten Produktionsorganismen werden in Bioreaktoren gezüchtet und anschließend
wird das gewünschte Produkt isoliert und gereinigt. Im Artikel wird insbesondere auf
Herstellung und klinischen Einsatz des rekombinanten Erythropoetins in der Nephrologie,
Hämatoonkologie und elektiver Chirugie eingegangen.
Genetically Engineered Drugs and their Application of Recombinant Erythropoietin.
Over the past two decades, many genetically engineered drugs have been developed and
approved for the treatment of patients. Typically, these drugs are characterized by
a high and specific activity in the presence of optimal safety. They include hormones,
enzymes, growth and coagulation factors, antibodies as well as vaccines. All these
proteins are generated using recombinant DNA technology. An expression vector with
the gene encoding for the protein of interest is introduced into an appropriate microorganism
or cell line. The biochemical machinery of the host cell then translates the genetic
information into the corresponding protein. Large scale production of the recombinant
drugs uses biotechnological processes. The genetically modified organisms are grown
in bioreactors from which the desired protein is finally isolated and purified. This
review focuses on the production and clinical application of recombinant erythropoietin
in the areas of nephrology, hemato-oncology and elective surgery.
Schlüsselwörter:
Erythropoetin - Rekombinante Arzneimittel - Gentechnik
Key words:
Erythropoietin - Recombinant drugs - Genetic engineering
Literatur
- 1
Neumann P, O'Shaughnessy M, Remis R, Tsoukas C, Lepine D, Davis M.
Laboratory evidence of active HIV-1 infection in Canadians with hemophilia associated
with administration of heat-treated factor VIII.
J Acquir Immune Defic Syndr.
1990;
3
278-281
- 2
Cohen S N, Chang A CY, Boyer H W, Helling R B.
Construction of biologically function al bacterial plasmids in vitro.
Proc Nat Acad Sci USA.
1973;
70
3240-3244
- 3 Dingermann T, Zündorf I.
Gentechnik-Biotechnik. Stuttgart,; Wiss. Verlagsgesellschaft mbH 1999
- 4
Brogard J M, Blickle J F, Paris-Bockel D.
Genetically engineered insulin: five years of experience.
Drugs Exp Clin Res.
1985;
11
397-406
- 5
Rudick R A, Ransohoff R M, Lee J C, Peppler R, Yu M, Mathisen P M, Tuohy V K.
In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple sclerosis.
Neurology.
1998;
50
1294-1300
- 6
Anderson J H, Brunelle R L, Koivisto V A, Trautmann M E, Vignati L, DiMarchi R.
Improved mealtime treatment of diabetes mellitus using an insulin analogue. Multicenter
Insulin Lispro Study Group.
Clin Ther.
1997;
19
62-72
- 7
Noble S, McTavish D.
Reteplase. A review of its pharmacological properties and clinical efficacy in the
management of acute myocardial infarction.
Drugs.
1996;
52
589-605
- 8
Honscha W.
Transgenic animals as bioreactors in the service of the pharmaceutical industry.
DTW Dtsch Tierärztl Wochenschr.
1999;
106
425-432
- 9
Kieber-Emmons T, Murali R, Greene M I.
Therapeutic peptides and peptidomimetics.
Curr Opin Biotechnol.
1997;
8
435-441
- 10
Barbone F P, Johnson D L, Farrell F X, Collins A, Middleton S A, McMahon F J, Tullai J,
Jolliffe L K.
New epoetin molecules and novel therapeutic approaches.
Nephrol Dial Transplant.
1999;
14
(Suppl. 2)
80-84
- 11
Sunder-Plassmann G, Hörl W.
Importance of iron supply for erythropoietin therapy.
Nephrol Dial Transplant.
1995;
10
2070-2076
- 12
Eschbach J, Kelly M, Haley N, Abels R, Adamson J.
Treatment of the anemia of progresive renal failure with recombinant human erythropoietin.
N Engl J Med.
1989;
321
158-163
- 13
Murphy S, Parfrey P.
Erythropoietin therapy in chronic uremia: the impact of normalization of hematocrit.
Hypertens.
1999;
8
573-578
- 14
Eckardt K.
Cardiovascular consequences of renal anaemia and erythropoietin therapy.
Nephrol Dial Transplant.
1999;
14
1317-1323
- 15
London G, Zins B, Pannier B, Naret C, Berthelot J, Jacquot C, Safar M, Drueke T.
Vascular changes in hemodialysis patients in response to recombinant human erythropoietin.
Kidney Int.
1989;
36
878-882
- 16
Glaspy J, Bukowski R, Steinberg D, Taylor C, Tchekmedyian S, Vadhan-Ray S.
Impact of therapy with epoetin alfa on clinical outcomes in patients with nonmyeloid
malignancies during cancer chemotherapy in community oncology practice.
J Clin Oncol.
1997;
15
1218-1234
- 17
Thews O, Koenig R, Kelleher D, Kutzner J, Vaupel P.
Enhanced radiosensitivity in experimental tumors following erythropoietin treatment
of chemotherapy-induced anaemia.
Br J Cancer.
1998;
78
752-756
- 18
Silver D, Piver S.
Effects of recombinant human erythropoietin on the antitumor effect of cisplatin in
SCID mice bearing human ovarian cancer: a possible oxygen effect.
Gynecol Oncol.
1999;
73
280-284
- 19
Sowade O, Warnke H, Sowade B, Franke W, Messinger D, Gross J.
Avoidance of allogeneic blood transfusion by treatment with Epoetin beta (recombinant
human erythropoietin) in patients undergoing open-heart surgery.
Blood.
1997;
89
411-418
- 20
Laupacis A, Fergusson D.
Erythropoietin to minimize perioperative blood transfusion: a systematic review of
randomized trials.
Transfusion Medicine.
1998;
8
309-317
- 21
Corwin H, Gettinger A, Rodriguez R, Pearl R, Gubler D, Enny C, Colton T, Corwin M.
Efficacy of rekombinant human erythropoietin in the critically ill patient: A randomized,
double-blind, placebo-controlled trial.
Crit Care Med.
1999;
27
2346-2350
- 22
Schreiber S, Howaldt S, Schnoor M, Nikolaus S, Bauditz J, Gasche C, Lochs H, Raedler A.
Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease.
N Engl J Med.
1996;
334
619-623
- 23
Peeters H, Jongen-Lavrencic M, Vreugdenhil G, Swaak A.
Effect of recombinant human erythropoietin on anaemia and disease activity in patients
with rheumatoid arthritis and anaemia of chronic disease.
Ann Rheumat Dis.
1996;
55
739-744
- 24
Maier R, Obladen M, Scigalla P, Lindenkamp O, Duc G, Hieronimi G, Halliday H, Versmold H,
Moriette G, Jorch G, Verellen G, Semmekrot B, Grauel G, Holland B.
The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion
in very-low-birthweight infants.
N Engl J Med.
1994;
330
1174-1179
- 25
Breymann C, Major A, Richter C, Huch R, Huch A.
Recombinant human erythropoietin in combination with parenteral iron in the treatment
of pregnancy anaemia: a pilot study.
J Perinat Med.
1995;
23
89-98
Dr. rer. nat. Verena Donatz
Janssen Cilag GmbH
Raiffeisenstraße 8
41470 Neuss