
<lom:lom xmlns:lom="https://oer-repo.uibk.ac.at/lom" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="https://oer-repo.uibk.ac.at/lom/latest https://w3id.org/oerbase/profiles/lomuibk/latest/schemas/lom-uibk.xsd">
  
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<lom:catalog>phaidra.vetmeduni.ac.at</lom:catalog>

  
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<lom:langstring xml:lang="x-none">o:4124</lom:langstring>

  
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<lom:identifier>
  
<lom:catalog>DOI</lom:catalog>

  
<lom:entry>
  
<lom:langstring xml:lang="x-none">10.1093/bjd/ljaf001</lom:langstring>

  
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</lom:identifier>

  
<lom:title>
  
<lom:langstring xml:lang="en">Preclinical in vitro and in vivo evidence for CD74-targeting as effective treatment strategy for cutaneous T cell lymphomas</lom:langstring>

  
</lom:title>

  
<lom:description>
  
<lom:langstring xml:lang="en">Prognosis and quality of life in patients with advanced cutaneous T-cell lymphoma (CTCL), particularly in those with Sézary syndrome (SS) or advanced-stage mycosis fungoides (MF), are poor. Monoclonal antibodies or antibody-drug conjugates (ADCs) have been added into CTCL treatment algorithms, but the spectrum of antibody-targetable cell surface antigens in T-cell non-Hodgkin lymphomas (T-NHLs) is limited.To evaluate the expression of the major histocompatibility complex class II chaperone CD74 in common subtypes of CTCL by various methods, and to explore the efficacy of targeting CD74 in CTCL cells with an anti-CD74 ADC in vitro and in vivo.We comprehensively investigated the expression of CD74 in well-defined CTCL cell lines by polymerase chain reaction, immunoblotting and flow cytometry. More than 140 primary CTCL samples of all common subtypes were analysed by immunohistochemistry, flow cytometry, immunofluorescence and &#39;co-detection by indexing&#39; (CODEX) multiplexed tissue imaging, as well as by single-cell RNA sequencing (scRNAseq) analyses. DNA methylation of CTCL cell lines was interrogated by the generation of genome-wide methylation profiling. The effect of a maytansinoid-conjugated humanized ADC against CD74 was investigated in CTCL cell lines in vitro, alone or in combination with gemcitabine, and in vivo after xenotransplantation of CTCL cell lines in NOD-scid Il2rgnull mice.We demonstrated that CD74 is widely and robustly expressed in CTCL cells. In addition, CD74 expression in SS and MF was confirmed by scRNAseq data analysis and was correlated in CTCL cell lines with CD74 DNA hypomethylation. CD74 was rapidly internalized in CTCL cells and CD74 targeting by the ADC STRO-001 efficiently killed CTCL-derived cell lines. Finally, targeting of CD74 synergized with conventional chemotherapy in vitro and eradicated murine xenotransplants of CTCL cell lines in vivo.CD74 is expressed in common CTCL subtypes. Targeting CD74 efficiently killed CTCL cells in vitro and in vivo. We therefore suggest the targeting of CD74 to be a highly promising treatment strategy for CTCL.</lom:langstring>

  
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<lom:language>eng</lom:language>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Monoclonal-Antibody Milatuzumab</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Invariant Chain</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Mycosis-Fungoides</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Sezary-Syndrome</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Anti-Cd74 Antibody</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Mif Receptor</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Brefeldin-A</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Phase-I</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Pralatrexate</lom:langstring>

  
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<lom:keyword>
  
<lom:langstring xml:lang="en">Organization</lom:langstring>

  
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<lom:datetime>2025-05-09T08:50:05.538Z</lom:datetime>

  
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<lom:langstring xml:lang="x-none">LOMv1.0</lom:langstring>

  
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VERSION:3.0
N:Costanza;Mariantonia;
FN:Mariantonia Costanza
END:VCARD</lom:vcard>

  
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N:Giordano;Catello;
FN:Catello Giordano
END:VCARD</lom:vcard>

  
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N:von Brünneck;Ann-Christin;
FN:Ann-Christin von Brünneck
END:VCARD</lom:vcard>

  
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<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Zhao;Jing;
FN:Jing Zhao
END:VCARD</lom:vcard>

  
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<lom:vcard>BEGIN:VCARD
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N:Makky;Ahmad;
FN:Ahmad Makky
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N:Vinh;Katharina;
FN:Katharina Vinh
END:VCARD</lom:vcard>

  
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N:Montes-Mojarro;Ivonne Aidee;
FN:Ivonne Aidee Montes-Mojarro
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<lom:centity>
  
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N:Reisinger;Florian;
FN:Florian Reisinger
END:VCARD</lom:vcard>

  
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<lom:centity>
  
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VERSION:3.0
N:Forchhammer;Stephan;
FN:Stephan Forchhammer
END:VCARD</lom:vcard>

  
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N:Witalisz-Siepracka;Agnieszka;
FN:Agnieszka Witalisz-Siepracka
END:VCARD</lom:vcard>

  
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<lom:centity>
  
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VERSION:3.0
N:Edtmayer;Sophie;
FN:Sophie Edtmayer
END:VCARD</lom:vcard>

  
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VERSION:3.0
N:Stoiber;Dagmar;
FN:Dagmar Stoiber
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Yin;Gang;
FN:Gang Yin
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
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N:Horst;David;
FN:David Horst
END:VCARD</lom:vcard>

  
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N:Fischer;Anja;
FN:Anja Fischer
END:VCARD</lom:vcard>

  
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N:Siebert;Reiner;
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N:Nicolay;Jan P.;
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END:VCARD</lom:vcard>

  
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<lom:centity>
  
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VERSION:3.0
N:Yin;Menghong;
FN:Menghong Yin
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Janz;Martin;
FN:Martin Janz
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Fend;Falko;
FN:Falko Fend
X-ORCID:https://orcid.org/0000-0002-5496-293X
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Becker;Jürgen C.;
FN:Jürgen C. Becker
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Schürch;Christian M.;
FN:Christian M. Schürch
END:VCARD</lom:vcard>

  
</lom:centity>

  
<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Kenner;Lukas;
FN:Lukas Kenner
X-ORCID:https://orcid.org/0000-0003-2184-1338
END:VCARD</lom:vcard>

  
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<lom:centity>
  
<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Assaf;Chalid;
FN:Chalid Assaf
END:VCARD</lom:vcard>

  
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<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Merkel;Olaf;
FN:Olaf Merkel
END:VCARD</lom:vcard>

  
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<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Mathas;Stephan;
FN:Stephan Mathas
END:VCARD</lom:vcard>

  
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