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Bertoni_2024_Wiley_Brit J Haematol_Targeting CD25 lymphoma
Journal article

Targeting CD25+ lymphoma cells with the antibody-drug conjugate camidanlumab tesirine as a single agent or in combination with targeted agents

  • Spriano, Filippo ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Tarantelli, Chiara ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Cascione, Luciano ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
  • Gaudio, Eugenio ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Golino, Gaetanina ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Scalise, Lorenzo Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Cacciapuoti, Maria Teresa Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, USA
  • Zucca, Emanuele ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
  • Stathis, Anastasios ORCID Department of Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland - Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Van Berkel, Patrick H. ADC Therapeutics (UK) Ltd., London, UK
  • Inghirami, Giorgio Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York,USA
  • Zammarchi, Francesca ADC Therapeutics (UK) Ltd., London, UK
  • Bertoni, Francesco ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Department of Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
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  • 2024
Published in:
  • British journal of haematology. - 2024, vol. 205, no. 5, p. 1873-1882
Antibody-drug conjugate
Camidanlumab tesirine
CD25
Lymphomas
T-cell lymphoma
English Camidanlumab tesirine (ADCT-301) is a CD25-specific antibody-drug conjugate (ADC) employing SG3199, a highly cytotoxic DNA minor groove cross-linking pyrrolobenzodiazepine dimer. The ADC has shown early clinical antitumour activity in various cancers, including B- and T-cell lymphomas. We assessed its preclinical activity as a single agent in 57 lymphoma cell lines and in combination with selected drugs in T-cell lymphoma-derived cell lines. Cells were exposed to increasing concentrations of the ADC or SG3199 for 96 h, followed by an MTT proliferation assay. CD25 expression was measured at cell surface and RNA levels. Experiments with PDX-derived cell lines were used for validation studies. Camidanlumab tesirine presented more potent single agent in vitro cytotoxic activity in T- than B-cell lymphomas. In vitro activity was correlated with CD25 cell surface and RNA expression. In vitro activity was correlated with CD25 cell surface and RNA expression. When camidanlumab tesirine-containing combinations were evaluated in four T-cell lymphoma models, the most active partners were everolimus, copanlisib, venetoclax, vorinostat, and pralatrexate, followed by bortezomib, romidepsin, bendamustine, and 5-azacytidine. The strong camidanlumab tesirine single-agent anti-lymphoma activity and the in vitro synergisms with targeted agents identify potential combination partners for future clinical studies.
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Language
  • English
Classification
Medicine
License
CC BY-NC-ND
Open access status
hybrid
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Persistent URL
https://n2t.net/ark:/12658/srd1330221
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