Kleine Antigene – große Wirkung

Zusammenfassung

Die allogene Blutstammzelltransplantation (HCT) ist oftmals die einzige kurative Behandlungsoption für Patienten mit malignen und nicht-malignen hämatologischen Erkrankungen. Nach der HCT richten sich immunologische, sogenannte Graft-versus-Leukämie (GvL)-Reaktionen gegen die bösartigen Zellen und tragen hocheffektiv zur Remission der Erkrankungen bei. Sowohl der GvL-Effekt, aber auch die Graft-versus-Host-Erkrankung (GvHD) werden nach HLA-identer HCT von Spender-T-Zellen vermittelt und resultieren aus Unterschieden der Minor Histokompatibilitätsantigene (mHag) zwischen Spender und Empfänger. GvL-Reaktionen können ebenfalls durch Tumor-spezifische immunogene Peptide ausgelöst werden, der Fokus soll in diesem Übersichtsartikel jedoch auf den mHag liegen. Wir möchten den aktuellen Kenntnissstand und am Beispiel des mHag HA-1 die daraus resultierenden therapeutischen Optionen vorstellen. Das mHag HA-1 ist das am besten erforschte mHag: es wird ausschließlich auf hämatopoetischen Zellen und aberrant auf einigen soliden Tumoren, nicht jedoch auf Zielzellen der GvHD exprimiert. Mit einer HA-1-spezifischen Immuntherapie wäre es möglich, den endogenen GvL-Effekt nach der HCT zu verstärken und selektiv HA-1-positive Leukämie- und Tumorzellen anzugreifen, ohne eine GvHD auszulösen. Das Spektrum einer möglichen therapeutischen Nutzung reicht von der Vakzinierung geeigneter Patienten- und Spenderpaare mit der immunogenen Variante des HA-1 Peptides, bis hin zur Applikation HA-1-spezifischer zytotoxischer T-Zellen (adoptive Immuntherapie).

Summary

Allogeneic hematopoietic cell transplantation (HCT) is often the only curative treatment option for patients with malignant and non-malignant hematological diseases. There is striking evidence that immunological Graft-versus-Leukemia (GvL)-reactions efficiently eradicate malignant cells after transplant. After HLA-matched HCT both the beneficial GvL-effect and the detrimental Graft-versus-Host Disease (GvHD) are mediated by donor derived T-cells specific for minor histocompatibility antigens (mHag) that differ between patient and stem cell donor. In addition, tumor-specific antigens can also be targeted and contribute to GvL-reactivity. This review summarizes the state-of-the-art knowledge on mHag and presents the potential therapeutical options on example of the mHag HA-1. HA-1 is currently the best characterized mHag and particularly attractive for immunotherapy due to the restricted expression on hematopoietic cells and on some solid tumors but not on cells involved during GvHD. This would allow amplifying the endogenous GvL-effect and selectively targeting malignant HA-1-positive cells without causing GvHD. HA-1-specific immunotherapy in eligible patient and donor pairs may range from vaccination with the immunogenic HA-1 peptide to the infusion of HA-1-specific cytotoxic T-cells (adoptive immunotherapy).

Schlüsselwörter

Allogene Blutstammzelltransplantation - Konditionierung mit reduzierter Intensität - Minor Histokompatibilitätsantigene - Graft-versus-Leukämie-Effekt - Graft-versus-Host-Erkrankung - GvHD

Key words

allogeneic hematopoietic cell transplantation - reduced intensity conditioning - minor histocompatibility antigens - graft-versus-leukemia-effect - graft-versus-host disease - GvHD

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