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Vaccine-induced T cell receptor T cell therapy targeting a glioblastoma stemness antigen

T cell receptor-engineered T cells (TCR-T) could be advantageous in glioblastoma by allowing safe and ubiquitous targeting of the glioblastoma-derived peptidome. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1), is a clinically targetable glioblastoma antigen associated with glioblastoma cell...

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Main Authors: Chih, Yu-Chan (Author) , Dietsch, Amelie C. (Author) , Koopmann, Philipp (Author) , Ma, Xiujian (Author) , Agardy, Dennis (Author) , Zhao, Binghao (Author) , De Roia, Alice (Author) , Kourtesakis, Alexandros (Author) , Kilian, Michael (Author) , Krämer, Christopher (Author) , Suwala, Abigail Kora (Author) , Stenzinger, Miriam (Author) , Boenig, Halvard (Author) , Blum, Agnieszka (Author) , Pienkowski, Victor Murcia (Author) , Aman, Kuralay (Author) , Becker, Jonas Philipp (Author) , Feldmann, Henrike (Author) , Bunse, Theresa (Author) , Harbottle, Richard P. (Author) , Riemer, Angelika (Author) , Liu, Hai-Kun (Author) , Etminan, Nima (Author) , Sahm, Felix (Author) , Ratliff, Miriam (Author) , Wick, Wolfgang (Author) , Platten, Michael (Author) , Green, Edward W. (Author) , Bunse, Lukas (Author)
Format: Article (Journal)
Language:English
Published: 01 February 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-16
ISSN:2041-1723
DOI:10.1038/s41467-025-56547-w
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-56547-w
Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41467-025-56547-w
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Author Notes:Yu-Chan Chih, Amelie C. Dietsch, Philipp Koopmann, Xiujian Ma, Dennis A. Agardy, Binghao Zhao, Alice De Roia, Alexandros Kourtesakis, Michael Kilian, Christopher Krämer, Abigail K. Suwala, Miriam Stenzinger, Halvard Boenig, Agnieszka Blum, Victor Murcia Pienkowski, Kuralay Aman, Jonas P. Becker, Henrike Feldmann, Theresa Bunse, Richard Harbottle, Angelika B. Riemer, Hai-Kun Liu, Nima Etminan, Felix Sahm, Miriam Ratliff, Wolfgang Wick, Michael Platten, Edward W. Green and Lukas Bunse
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Summary:T cell receptor-engineered T cells (TCR-T) could be advantageous in glioblastoma by allowing safe and ubiquitous targeting of the glioblastoma-derived peptidome. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1), is a clinically targetable glioblastoma antigen associated with glioblastoma cell stemness. Here, we identify a therapeutic HLA-A*02-restricted PTPRZ1-reactive TCR retrieved from a vaccinated glioblastoma patient. Single-cell sequencing of primary brain tumors shows PTPRZ1 overexpression in malignant cells, especially in glioblastoma stem cells (GSCs) and astrocyte-like cells. The validated vaccine-induced TCR recognizes the endogenously processed antigen without off-target cross-reactivity. PTPRZ1-specific TCR-T (PTPRZ1-TCR-T) kill target cells antigen-specifically, and in murine experimental brain tumors, their combined intravenous and intracerebroventricular administration is efficacious. PTPRZ1-TCR-T maintain stem cell memory phenotype in vitro and in vivo and lyse all examined HLA-A*02+ primary glioblastoma cell lines with a preference for GSCs and astrocyte-like cells. In summary, we demonstrate the proof of principle to employ TCR-T to treat glioblastoma.
Item Description:Gesehen am 08.07.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-56547-w

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