%0 Journal Article
%A Chih, Yu-Chan
%A Dietsch, Amelie C
%A Koopmann, Philipp
%A Ma, Xiujian
%A Agardy, Dennis Alexander
%A Zhao, Binghao
%A De Roia, Alice
%A Kourtesakis, Alexandros
%A Kilian, Michael
%A Krämer, Christopher
%A Suwala, Abigail K
%A Stenzinger, Miriam
%A Boenig, Halvard
%A Blum, Agnieszka
%A Pienkowski, Victor Murcia
%A Aman, Kuralay
%A Becker, Jonas
%A Feldmann, Henrike
%A Bunse, Theresa
%A Harbottle, Richard
%A Riemer, Angelika
%A Liu, Haikun
%A Etminan, Nima
%A Sahm, Felix
%A Ratliff, Miriam
%A Wick, Wolfgang
%A Platten, Michael
%A Green, Edward
%A Bunse, Lukas
%T Vaccine-induced T cell receptor T cell therapy targeting a glioblastoma stemness antigen.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DKFZ-2025-00269
%P 1262
%D 2025
%Z #EA:D170#LA:D170# / DKFZ-ZMBH-Alliance / HI-TRON
%X 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.
%K Glioblastoma: therapy
%K Glioblastoma: immunology
%K Humans
%K Animals
%K Receptors, Antigen, T-Cell: immunology
%K Receptors, Antigen, T-Cell: metabolism
%K Brain Neoplasms: immunology
%K Brain Neoplasms: therapy
%K Mice
%K Neoplastic Stem Cells: immunology
%K Neoplastic Stem Cells: metabolism
%K Cell Line, Tumor
%K Cancer Vaccines: immunology
%K HLA-A2 Antigen: immunology
%K HLA-A2 Antigen: metabolism
%K HLA-A2 Antigen: genetics
%K T-Lymphocytes: immunology
%K T-Lymphocytes: metabolism
%K Immunotherapy, Adoptive: methods
%K Receptor-Like Protein Tyrosine Phosphatases, Class 5: metabolism
%K Receptor-Like Protein Tyrosine Phosphatases, Class 5: genetics
%K Antigens, Neoplasm: immunology
%K Antigens, Neoplasm: metabolism
%K Female
%K Receptors, Antigen, T-Cell (NLM Chemicals)
%K Cancer Vaccines (NLM Chemicals)
%K PTPRZ1 protein, human (NLM Chemicals)
%K HLA-A2 Antigen (NLM Chemicals)
%K Receptor-Like Protein Tyrosine Phosphatases, Class 5 (NLM Chemicals)
%K HLA-A*02 antigen (NLM Chemicals)
%K Antigens, Neoplasm (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39893177
%2 pmc:PMC11787355
%R 10.1038/s41467-025-56547-w
%U https://inrepo02.dkfz.de/record/298413