Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation

• Verfasst von: Casalegno Garduño, Rosaely [VerfasserIn]
• Verfasst von: Schmitt, Anita [VerfasserIn]
• Verfasst von: Spitschak, Alf [VerfasserIn]
• Verfasst von: Greiner, Jochen [VerfasserIn]
• Verfasst von: Wang, Lei [VerfasserIn]
• Verfasst von: Hilgendorf, Inken [VerfasserIn]
• Verfasst von: Hirt, Carsten [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Freund, Mathias [VerfasserIn]
• Verfasst von: Schmitt, Michael [VerfasserIn]
• Titel: Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation
• Verf.angabe: Rosaely Casalegno‐Garduño, Anita Schmitt, Alf Spitschak, Jochen Greiner, Lei Wang, Inken Hilgendorf, Carsten Hirt, Anthony D. Ho, Mathias Freund and Michael Schmitt
• Jahr: 2016
• Jahr des Originals: 2015
• Umfang: 10 S.
• Fussnoten: Online 31 October 2015 ; Gesehen am 13.02.2020
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2016
• Band/Heft Quelle: 138(2016), 7, Seite 1792-1801
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.29909
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AML
• Sach-SW: MDS
• Sach-SW: specific T cells
• Sach-SW: WT1
• K10plus-PPN: 1689992824

Abstract

Wilms' tumor gene 1 (WT1) is overexpressed in leukemia and WT1-derived CD8+ T-cell epitopes for immunotherapies targeting WT1 have been defined. Here, we analyzed expression of WT1 in 226 peripheral blood and bone marrow samples from patients with acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) before and after allogeneic stem cell transplantation (SCT). Transcripts were assessed by quantitative polymerase chain reaction, and WT1-specific CD8+ cytotoxic T cells (CTL) were monitored by tetramer staining and enzyme-linked immunospot (ELISPOT) assays. Reduction of WT1 levels correlated with a longer survival (p < 0.01). Increment of WT1 transcripts eventually resulted in relapse and subsequent death of the patients. In patients with longer survival and continuous complete remission (cCR) after SCT, higher and enduring frequencies of WT1-specific CTL than in patients developing a relapse were detected. These cells were effector T cells secreting interferon gamma and granzyme B. In summary, WT1 is a suitable marker for the detection of minimal residual disease after SCT or chemotherapy. A rising WT1 signal correlated with a dismal prognosis of the patients. WT1-specific CD8+ T cells might contribute to the maintenance of a cCR. Targeting WT-1 by peptide/protein vaccination as well as adoptive transfer of genetically modified T cells are future options in the individualized therapy for AML/MDS patients.