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Infektionen und Immuntherapie

Adoptiver Transfer antigenspezifischer T-Zellen bei Infektionen nach allogener Stammzelltransplantation

Infections after allogeneic stem cell transplantation

Treatment by adoptive transfer of antigen-specific T cells

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Zusammenfassung

Die allogene Stammzelltransplantation (SZT) führt zu einer transienten Immunsuppression, in der Virus- und Pilzinfektionen lebensbedrohlich verlaufen können. Verbesserte SZT-Regimes und Supportivmaßnahmen konnten die Infektionsraten senken, für die Kontrolle der Infektionen ist jedoch eine funktionelle T-Zell-Antwort essenziell. Adeno-, Zytomegalie- und Epstein-Barr-Viren reaktivieren meist endogen, während Aspergillusinfektionen v. a. exogen entstehen. Die Transfusion erregerspezifischer T-Zellen eines gesunden Spenders in einen erkrankten Empfänger stellt eine viel versprechende neue Therapieform dar, um adaptive Immunität auf den Empfänger zu übertragen. Eine Isolierung spezifischer T-Zellen ist notwendig, um alloreaktive T-Zellen zu depletieren und damit das Risiko einer komplikationsreichen Graft-versus-Host-Erkrankung zu minimieren. Adoptiver T-Zell-Transfer wurde bisher in aufwändigen Protokollen bei Virusinfektionen nach allogener SZT durchgeführt. Aufbauend auf aktuellen Grundlagenerkenntnissen zielen neue Methoden auf eine prompte Verfügbarkeit passender T-Zell-Präparate ab. Darüber hinaus bleiben das Verständnis und die gezielte Manipulation der T-Zell-Antwort als Therapieverfahren eine Herausforderung.

Abstract

Allogeneic stem cell transplantation (SCT) can expose patients to a transient but marked immunosuppression, during which viral and fungal infections are an important cause of morbidity and mortality. Control of these infections ultimately depends on restoring adequate T-cell immunity. Most viral infections after SCT are caused by the endogenous reactivation of persistent pathogens such as adenovirus (ADV), cytomegalovirus (CMV), and Epstein-Barr-virus (EBV), whereas invasive infections due to Aspergillus spp. are mostly exogenous. Cellular immunotherapy is an attractive approach to enable immune protection of the host. The isolation of pathogen-specific T cells from a healthy donor and their infusion into a recipient is done by a procedure known as adoptive T-cell transfer. The separation of pathogen-specific T cells is necessary to deplete alloreactive T cells and avoid graft-versus-host disease. Adoptive T-cell transfer has been performed after allogeneic SCT in many patients with CMV, EBV, and ADV infections using time- and labour-consuming protocols. Based on basic research, new immunotherapeutic protocols aim at a broader and faster availability of adoptive T-cell transfer. However, the manipulation of antigen-specific T-cell responses as a treatment approach remains an ongoing challenge.

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Authors and Affiliations

  1. Abteilung für pädiatrische Hämatologie/Onkologie, Universitätsklinik für Kinderheilkunde und Jugendmedizin Tübingen, Hoppe-Seyler-Straße 1, 72076, Tübingen, Deutschland

    T. Feuchtinger

  2. Klinik für Kinder- und Jugendmedizin, Technische Universität München, München, Deutschland

    U. Behrends

  3. Universitätsklinik für Kinder- und Jugendmedizin Frankfurt, Frankfurt, Deutschland

    T. Lehrnbecher

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  1. T. Feuchtinger
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Correspondence to T. Feuchtinger.

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Feuchtinger, T., Behrends, U. & Lehrnbecher, T. Infektionen und Immuntherapie. Monatsschr Kinderheilkd 158, 246–253 (2010). https://doi.org/10.1007/s00112-009-2142-3

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