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@ARTICLE{Chih:298413,
      author       = {Y.-C. Chih$^*$ and A. C. Dietsch$^*$ and P. Koopmann$^*$
                      and X. Ma$^*$ and D. A. Agardy$^*$ and B. Zhao$^*$ and A. De
                      Roia$^*$ and A. Kourtesakis$^*$ and M. Kilian$^*$ and C.
                      Krämer$^*$ and A. K. Suwala$^*$ and M. Stenzinger and H.
                      Boenig and A. Blum and V. M. Pienkowski and K. Aman$^*$ and
                      J. Becker$^*$ and H. Feldmann$^*$ and T. Bunse$^*$ and R.
                      Harbottle$^*$ and A. Riemer$^*$ and H. Liu$^*$ and N.
                      Etminan and F. Sahm$^*$ and M. Ratliff$^*$ and W. Wick$^*$
                      and M. Platten$^*$ and E. Green$^*$ and L. Bunse$^*$},
      title        = {{V}accine-induced {T} cell receptor {T} cell therapy
                      targeting a glioblastoma stemness antigen.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-00269},
      pages        = {1262},
      year         = {2025},
      note         = {#EA:D170#LA:D170# / DKFZ-ZMBH-Alliance / HI-TRON},
      abstract     = {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.},
      keywords     = {Glioblastoma: therapy / Glioblastoma: immunology / Humans /
                      Animals / Receptors, Antigen, T-Cell: immunology /
                      Receptors, Antigen, T-Cell: metabolism / Brain Neoplasms:
                      immunology / Brain Neoplasms: therapy / Mice / Neoplastic
                      Stem Cells: immunology / Neoplastic Stem Cells: metabolism /
                      Cell Line, Tumor / Cancer Vaccines: immunology / HLA-A2
                      Antigen: immunology / HLA-A2 Antigen: metabolism / HLA-A2
                      Antigen: genetics / T-Lymphocytes: immunology /
                      T-Lymphocytes: metabolism / Immunotherapy, Adoptive: methods
                      / Receptor-Like Protein Tyrosine Phosphatases, Class 5:
                      metabolism / Receptor-Like Protein Tyrosine Phosphatases,
                      Class 5: genetics / Antigens, Neoplasm: immunology /
                      Antigens, Neoplasm: metabolism / Female / Receptors,
                      Antigen, T-Cell (NLM Chemicals) / Cancer Vaccines (NLM
                      Chemicals) / PTPRZ1 protein, human (NLM Chemicals) / HLA-A2
                      Antigen (NLM Chemicals) / Receptor-Like Protein Tyrosine
                      Phosphatases, Class 5 (NLM Chemicals) / HLA-A*02 antigen
                      (NLM Chemicals) / Antigens, Neoplasm (NLM Chemicals)},
      cin          = {D170 / HD01 / A240 / D420 / B320 / B300 / D410},
      ddc          = {500},
      cid          = {I:(DE-He78)D170-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)A240-20160331 / I:(DE-He78)D420-20160331 /
                      I:(DE-He78)B320-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)D410-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39893177},
      pmc          = {pmc:PMC11787355},
      doi          = {10.1038/s41467-025-56547-w},
      url          = {https://inrepo02.dkfz.de/record/298413},
}