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@ARTICLE{Kourtesakis:302114,
      author       = {A. Kourtesakis$^*$ and E. Bailey$^*$ and H. N. H. Chow$^*$
                      and H. Rohdjeß$^*$ and N. Mussnig$^*$ and D. A. Agardy$^*$
                      and D. C. F. Hoffmann$^*$ and Y.-C. Chih$^*$ and R. Will$^*$
                      and L. Kaulen$^*$ and M. Hahn$^*$ and R. Wagener$^*$ and D.
                      Reibold$^*$ and S. Pusch$^*$ and F. Sahm$^*$ and T. Sauer
                      and M. Schmitt and L. Bunse$^*$ and M. Platten$^*$ and W.
                      Wick$^*$ and T. Kessler$^*$},
      title        = {{U}tilization of universal-targeting m{SA}2 {CAR}-{T} cells
                      for the treatment of glioblastoma.},
      journal      = {OncoImmunology},
      volume       = {14},
      number       = {1},
      issn         = {2162-4011},
      address      = {Abingdon},
      publisher    = {Taylor $\&$ Franics},
      reportid     = {DKFZ-2025-01246},
      pages        = {2518631},
      year         = {2025},
      note         = {#EA:B320#LA:B320#},
      abstract     = {Glioblastoma (GB) remains refractory to chimeric antigen
                      receptor (CAR)-T cell therapy, mainly attributed to tumor
                      heterogeneity and antigen escape. CAR-T cells utilizing
                      monomeric streptavidin-2 (mSA2) instead of a traditional
                      target binding domain, bind biotinylated antibodies and can
                      be directed to variable targets to mediate anti-tumor
                      effects. Although such an approach might circumvent the
                      aforementioned challenges, the potential of mSA2 CAR-T cells
                      for brain tumor treatment remains unexplored. In this study,
                      we generated mSA2 CAR-T cells and tested their efficacy
                      against GB by tailoring their specificity toward
                      GB-associated markers CD276, EPHA2, CD70 and IL13Ra2. In
                      vitro, mSA2 CAR-T cells specifically recognized multiple
                      primary GB cell lines in a target- and biotinylated
                      antibody-dependent manner. Moreover, in heterogenous tumor
                      environments, mSA2 CAR-T cells simultaneously targeted
                      multiple subpopulations, guided by combinations of
                      biotinylated antibodies, indicating their potential to
                      address tumor heterogeneity. Finally, the mSA2 CAR-T
                      cell-mediated anti-tumor functions were demonstrated in
                      vivo. Immunocompromised mice orthotopically implanted with
                      CD70+ or CD276+ GB cells and treated with mSA2 CAR-T cells
                      pre-armed with antibodies against these two antigens
                      exhibited control of tumor growth and induction of GB cell
                      apoptosis after therapy. Taken together, our study suggests
                      that antibody-guided mSA2 CAR-T cells can target potentially
                      any surface GB-related antigen both in vitro and in vivo,
                      either univalently or multivalently, with underlined
                      clinical implications.},
      keywords     = {Glioblastoma: therapy / Glioblastoma: immunology /
                      Glioblastoma: pathology / Animals / Humans / Mice /
                      Immunotherapy, Adoptive: methods / Brain Neoplasms: therapy
                      / Brain Neoplasms: immunology / Brain Neoplasms: pathology /
                      Receptors, Chimeric Antigen: immunology / Receptors,
                      Chimeric Antigen: metabolism / Receptors, Chimeric Antigen:
                      genetics / Cell Line, Tumor / Xenograft Model Antitumor
                      Assays / T-Lymphocytes: immunology / T-Lymphocytes:
                      metabolism / Glioblastoma (Other) / immunotherapy (Other) /
                      mSA2 CAR-T cells (Other) / universal antigen targeting
                      (Other) / Receptors, Chimeric Antigen (NLM Chemicals)},
      cin          = {B320 / HD01 / D170 / W111 / B300},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)D170-20160331 / I:(DE-He78)W111-20160331 /
                      I:(DE-He78)B300-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40518621},
      doi          = {10.1080/2162402X.2025.2518631},
      url          = {https://inrepo02.dkfz.de/record/302114},
}