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@ARTICLE{Krmer:282891,
      author       = {C. Krämer$^*$ and M. Kilian$^*$ and Y. C. Chih$^*$ and A.
                      Kourtesakis$^*$ and D. C. Hoffmann$^*$ and T. Boschert$^*$
                      and P. Koopmann$^*$ and K. Sanghvi$^*$ and A. De Roia$^*$
                      and S. Jung$^*$ and K. Jähne$^*$ and B. Day and L. D.
                      Shultz and M. Ratliff and R. Harbottle$^*$ and E. W.
                      Green$^*$ and R. Will$^*$ and W. Wick$^*$ and M. Platten$^*$
                      and L. Bunse$^*$},
      title        = {{NLGN}4{X} {TCR} transgenic {T} cells to treat gliomas.},
      journal      = {Neuro-Oncology},
      volume       = {26},
      number       = {2},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2023-01884},
      pages        = {266-278},
      year         = {2024},
      note         = {HI-TRON / #EA:D170#LA:D170# / 2024 Feb 2;26(2):266-278},
      abstract     = {Neuroligin 4 X-linked (NLGN4X) harbors a human leukocyte
                      antigen (HLA)-A2-restricted tumor-associated antigen,
                      overexpressed in human gliomas, that was found to induce
                      specific cytotoxic T cell responses following multi-peptide
                      vaccination in patients with newly- diagnosed glioblastoma.T
                      cell receptor (TCR) discovery was performed using
                      droplet-based single cell TCR sequencing of
                      NLGN4X-tetramer-sorted T cells post vaccination. The
                      identified TCR was delivered to Jurkat T cells and primary
                      human T cells (NLGN4X-TCR-T). Functional profiling of
                      NLGN4X-TCR-T was performed by flow cytometry and
                      cytotoxicity assays. Therapeutic efficacy of
                      intracerebroventricular NLGN4X-TCR-T was assessed in NOD
                      scid gamma (NSG) major histocompatibility complex (MHC) I/II
                      knockout (KO) (NSG MHC I/II KO) mice bearing
                      NLGN4X-expressing experimental gliomas.An HLA-A
                      *02-restricted vaccine-induced T cell receptor specifically
                      binding NLGN4X131-139 was applied for therapeutic use.
                      Reactivity, cytotoxicity, and polyfunctionality of this
                      NLGN4X-specific TCR is demonstrated in various cellular
                      models. Intracerebroventricular administration of
                      NLGN4X-TCR-T prolongs survival and leads to an objective
                      response rate (ORR) of 44.4 $\%$ in experimental
                      gliomas-bearing NSG MHC I/II KO mice compared to 0.0 $\%$ in
                      control groups, respectively.NLGN4X-TCR-T demonstrates
                      efficacy in a preclinical glioblastoma model. On a global
                      scale, we provide first evidence for the therapeutic
                      retrieval of vaccine-induced human TCRs for the
                      off-the-shelf treatment of glioblastoma patients.},
      cin          = {D170 / HD01 / B320 / F160 / W111},
      ddc          = {610},
      cid          = {I:(DE-He78)D170-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B320-20160331 / I:(DE-He78)F160-20160331 /
                      I:(DE-He78)W111-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37715782},
      doi          = {10.1093/neuonc/noad172},
      url          = {https://inrepo02.dkfz.de/record/282891},
}