Definition and characterization of SOX11-derived T cell epitopes towards immunotherapy of glioma

The transcription factor SOX11 is a tumor-associated antigen with low expression in normal cells, but overexpression in glioblastoma (GBM). So far, conventional surgery, chemotherapy, and radiotherapy have not substantially improved the dismal prognosis of relapsed/refractory GBM patients. Immunothe...

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Hauptverfasser: Liu, Yibin (VerfasserIn) , Keib, Anna (VerfasserIn) , Neuber, Brigitte (VerfasserIn) , Wang, Lei (VerfasserIn) , Riemer, Angelika (VerfasserIn) , Bonsack, Maria (VerfasserIn) , Hückelhoven-Krauss, Angela (VerfasserIn) , Schmitt, Anita (VerfasserIn) , Müller-Tidow, Carsten (VerfasserIn) , Schmitt, Michael (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 18 January 2023
In: International journal of molecular sciences
Year: 2023, Jahrgang: 24, Heft: 3, Pages: 1-18
ISSN:1422-0067
DOI:10.3390/ijms24031943
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ijms24031943
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1422-0067/24/3/1943
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Verfasserangaben:Yibin Liu, Anna Keib, Brigitte Neuber, Lei Wang, Angelika B. Riemer, Maria Bonsack, Angela Hückelhoven-Krauss, Anita Schmitt, Carsten Müller-Tidow and Michael Schmitt

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520 |a The transcription factor SOX11 is a tumor-associated antigen with low expression in normal cells, but overexpression in glioblastoma (GBM). So far, conventional surgery, chemotherapy, and radiotherapy have not substantially improved the dismal prognosis of relapsed/refractory GBM patients. Immunotherapy is considered a promising strategy against GBM, but there is a fervent need for better immunotargets in GBM. To this end, we performed an in silico prediction study on SOX11, which primarily yielded ten promising HLA-A*0201-restricted peptides derived from SOX11. We defined a novel peptide FMACSPVAL, which had the highest score according to in silico prediction (6.02 nM by NetMHC-4.0) and showed an exquisite binding affinity to the HLA-A*0201 molecule in the peptide-binding assays. In the IFN-γ ELISPOT assays, FMACSPVAL demonstrated a high efficiency for generating SOX11-specific CD8+ T cells. Nine out of thirty-two healthy donors showed a positive response to SOX11, as assessed by the ELISPOT assays. Therefore, this novel antigen peptide epitope seems to be promising as a target for T cell-based immunotherapy in GBM. The adoptive transfer of in vitro elicited SOX11-specific CD8+ T cells constitutes a potential approach for the treatment of GBM patients. 
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