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Xenogene Zelltherapeutika

Behandlung von Typ 1 Diabetes mittels porciner Pankreasinseln und -inselzellen

Xenogeneic cell therapeutics

Treatment of type 1 diabetes using porcine pancreatic islets and islet cells

Zusammenfassung

Angesichts der bestehenden Knappheit an humanen Spenderorganen und -geweben kann die Entwicklung xenogener Zelltherapeutika (xZT) eine adäquate Behandlungsalternative sein. Insbesondere porcine Pankreasinseln und -inselzellen haben bereits zum jetzigen Zeitpunkt Eingang in die experimentelle Therapie von Typ 1 Diabetes mellitus (T1DM)-Patienten gefunden. Dabei stellen xZT sowohl aus medizinischer als auch aus ethischer und regulatorischer Sicht eine Herausforderung dar. So ist infolge der speziesübergreifenden Transplantation (Xenotransplantation) neben dem Risiko der immunologischen Abstoßung auch das Infektionsrisiko durch Übertragung von mikrobiellen und viralen Erregern zu berücksichtigen. Letzteres ist bidirektional und betrifft sowohl die Transmission vom Transplantat auf den Empfänger als auch die Transmission vom Empfänger auf das Transplantat. Die Überschreitung der Speziesbarriere erfordert eine kritische Nutzen-Risiko-Bewertung und nach Abschluss der Behandlung eine sorgfältige und langfristige Überwachung der Patienten. Die internationalen rechtlichen und regulatorischen Anforderungen an xZT basieren u. a. auf den von der Weltgesundheitsorganisation (WHO) 2008 im Changsha Kommuniqué formulierten Kriterien, die in Europa nach Inkraftsetzen der EU-Verordnung über Arzneimittel für neuartige Therapien (ATMP) im Leitfaden für xenogene Zelltherapeutika seitens der Europäischen Arzneimittelbehörde EMA mit abgebildet sind.

Abstract

In view of the existing shortage of human donor organs and tissues, xenogeneic cell therapeutics (xCT) offer an alternative for adequate treatment. In particular, porcine pancreatic islets and islet cells have already entered the field of experimental therapy for type-1 diabetes mellitus (T1DM) patients. Thereby, xCT depict challenging products with a glance on medical, ethical, and regulatory questions. With cross-species transplantation (xenotransplantation), the risk of immunological graft rejection as well as the risk of infectious transmission of microbial and viral pathogens must be considered. This includes the bidirectional transmission of microorganisms from graft to host as well as from host to graft. Crossing the border of species requires a critical risk-benefit evaluation as well as a thorough longtime surveillance of transplant recipients after treatment. The international legal and regulatory requirements for xCT are inter alia based on the World Health Organization criteria summarized in the Changsha Communiqué (2008). In the European Union, they were reflected by the European Medicines Agency (EMA) Guideline on Xenogeneic Cell-based Medicinal Products following the implementation of the Regulation on Advanced Therapies (ATMP). On the basis of this regulation, the first non-clinical and clinical experiences were obtained for porcine islets. The results suggest that supportive treatment of T1DM risk patients with xCT may be an alternative to established allogeneic organ transplantation in the future.

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Correspondence to Antonia W. Godehardt.

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Interessenkonflikt

Frau Dr. Antonia W. Godehardt wird gefördert durch die Mittel der Deutschen Forschungsgemeinschaft, DFG, SFB TRR CRC 127, Bonn, Deutschland.

Seitens der Autoren Frau Dr. Dagmar Schilling-Leiß und Herr Dr. Ralf Sanzenbacher besteht kein Interessenkonflikt.

Herr Prof. Dr. Ralf R. Tönjes ist Projektleiter des Projekts Z2 der DFG, SFB TRR CRC 127, Bonn, Deutschland.

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Godehardt, A., Schilling-Leiß, D., Sanzenbacher, R. et al. Xenogene Zelltherapeutika. Bundesgesundheitsbl. 58, 1281–1288 (2015). https://doi.org/10.1007/s00103-015-2246-y

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Schlüsselwörter

  • Xenogene Zelltherapeutika (xZT)
  • Xenotransplantation
  • Porcine Pankreasinseln
  • Xenozoonosen
  • Typ 1 Diabetes mellitus

Keywords

  • Xenogeneic cell therapeutics (xCT)
  • Xenotransplantation
  • Porcine pancreatic islets
  • Xenozoonosis
  • Type 1 diabetes mellitus