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@ARTICLE{Costanza:299525,
      author       = {M. Costanza and C. Giordano and A.-C. von Brünneck and J.
                      Zhao and A. Makky and K. Vinh and I. A. Montes-Mojarro and
                      F. Reisinger and S. Forchhammer$^*$ and A.
                      Witalisz-Siepracka and S. Edtmayer and D. Stoiber and G. Yin
                      and D. Horst$^*$ and A. Fischer and R. Siebert and J. P.
                      Nicolay$^*$ and M. Yin$^*$ and M. Janz and F. Fend$^*$ and
                      J. C. Becker$^*$ and C. M. Schürch$^*$ and L. Kenner and C.
                      Assaf and O. Merkel and S. Mathas$^*$},
      title        = {{P}reclinical in vitro and in vivo evidence for
                      {CD}74-targeting as effective treatment strategy for
                      cutaneous {T} cell lymphomas.},
      journal      = {British journal of dermatology},
      volume       = {192},
      number       = {5},
      issn         = {0366-2845},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2025-00483},
      pages        = {883-895},
      year         = {2025},
      note         = {2025 Apr 28;192(5):883-895},
      abstract     = {Prognosis and quality of life of advanced cutaneous T cell
                      lymphoma (CTCL) patients, in particular those with Sézary
                      syndrome (SS) and advanced-stage mycosis fungoides (MF), are
                      poor. Monoclonal antibodies or antibody-drug conjugates
                      (ADCs) have been implemented into CTCL therapy algorithms,
                      but the spectrum of antibody-targetable cell-surface
                      antigens on T cell non-Hodgkin lymphomas (T-NHL) is
                      limited.To evaluate expression of the MHC-II chaperone CD74
                      across common subtypes of CTCL by various methods, and to
                      explore the efficacy of CD74-targeting of CTCL cells by
                      anti-CD74 antibody-drug conjugate (ADC) in vitro and in
                      vivo.We comprehensively investigate expression of CD74 in
                      well-defined CTCL cell lines by PCR analyses, immunoblotting
                      and flow cytometry. More than 140 primary CTCL samples of
                      all common entities are analyzed by immunohistochemistry,
                      flow cytometry, immunofluorescence and 'co-detection by
                      indexing' (CODEX) multiplexed tissue imaging as well as
                      single-cell RNAseq analyses. DNA methylation of CTCL cell
                      lines is interrogated by generation of genome-wide
                      methylation profiling. The effect of a
                      maytansinoid-conjugated humanized ADC against CD74 is
                      investigated on CTCL cell lines in vitro, alone or in
                      combination with gemcitabine, and in vivo after
                      xenotransplantation of CTCL cell lines in NOD-scid Il2rgnull
                      (NSG) mice.We demonstrate by different experimental
                      approaches in CTCL cell lines and a broad collection of
                      primary CTCL samples that CD74 is widely and robustly
                      expressed in CTCL cells. Additionally, CD74 expression in SS
                      and MF is confirmed by analyses of single cell (sc)RNA-seq
                      data, and correlates in CTCL cell lines with CD74 gene DNA
                      hypomethylation. CD74 is rapidly internalized in CTCL cells,
                      and CD74 targeting by the ADC STRO-001 efficiently kills
                      CTCL-derived cell lines. Finally, CD74 targeting synergizes
                      with conventional chemotherapy in vitro, and eradicates
                      murine xenotransplants of CTCL cell lines in vivo.CD74 is
                      expressed across common CTCL subtypes, and CD74-targeting
                      efficiently kills CTCL cells in vitro and in vivo. Our data
                      thus identify CD74-targeting as highly promising treatment
                      strategy for CTCL.},
      cin          = {TU01 / BE01 / A370 / HD01 / ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)TU01-20160331 / I:(DE-He78)BE01-20160331 /
                      I:(DE-He78)A370-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)ED01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40036608},
      doi          = {10.1093/bjd/ljaf001},
      url          = {https://inrepo02.dkfz.de/record/299525},
}