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@ARTICLE{Poelchen:302016,
      author       = {J. Poelchen$^*$ and S. Pardo$^*$ and D. Novak$^*$ and Q.
                      Sun$^*$ and T. Steinfass$^*$ and M. Vierthaler$^*$ and Ö.
                      Cicek Sener$^*$ and K. Granados Blanco$^*$ and Y. Wang$^*$
                      and J. P. Nicolay$^*$ and P. Guermonprez and R.
                      Harbottle$^*$ and V. Umansky$^*$ and J. Utikal$^*$},
      title        = {{G}eneration and functional analysis of melanoma
                      antigen-specific {CD}8+ {T} cells derived from {S}/{MAR}
                      vector-transfected human induced pluripotent stem cells.},
      journal      = {International journal of cancer},
      volume       = {157},
      number       = {9},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2025-01214},
      pages        = {1876-1887},
      year         = {2025},
      note         = {#EA:A370#LA:A370# / 2025 Nov 1;157(9):1876-1887},
      abstract     = {Melanoma accounts for the majority of all skin
                      cancer-related deaths with rising incidence rates. Adoptive
                      cell therapies (ACT) with tumor antigen-specific CD8+ T
                      cells derived from human-induced pluripotent stem cells
                      (hiPSCs) might offer a promising treatment strategy for
                      advanced malignant melanoma patients. In this study, we
                      investigated two strategies for the generation of CD8+ T
                      cells from hiPSCs expressing a T cell receptor (TCR)
                      specific for the melanoma-associated antigen recognized by T
                      cells (MART-1) or a chimeric antigen receptor (CAR) specific
                      for the melanoma-associated chondroitin sulfate proteoglycan
                      (MCSP), respectively. While the long-term co-culture of
                      bioengineered OP9 stromal cells with CD34+ hematopoietic
                      stem/progenitor cells (HSPCs) facilitated the generation of
                      CD4 + CD8+ double-positive (DP) T cells, we encountered
                      difficulties in obtaining high percentages of CD8+
                      single-positive (SP) T cells using this method. However, the
                      replacement of the OP9 cells with a T cell differentiation
                      kit enabled the generation of CD8+ SP T cells after 47 days.
                      Despite a low expression of the T cell marker CD3 on the
                      surface of the generated CD8+ SP T cells, we detected
                      intracellular IFN-γ and surface CD107a expression upon
                      stimulation. Moreover, the generated CD8+ SP T cells
                      exhibited cytotoxic effects when co-cultured with melanoma
                      cell lines. The use of scaffold/matrix attachment region
                      (S/MAR) DNA vectors ensured persistent expression of the TCR
                      or the CAR during differentiation of T cells. Hence, these
                      findings demonstrate the potential as well as the challenges
                      associated with using S/MAR DNA vector-transfected hiPSCs
                      for the generation of melanoma antigen-specific CD8+ T
                      cells.},
      keywords     = {T cells (Other) / adoptive cell therapy (Other) / hiPSCs.
                      S/MAR vector (Other) / melanoma (Other)},
      cin          = {A370 / D420},
      ddc          = {610},
      cid          = {I:(DE-He78)A370-20160331 / I:(DE-He78)D420-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40504044},
      doi          = {10.1002/ijc.35524},
      url          = {https://inrepo02.dkfz.de/record/302016},
}