Targeting CD25+ lymphoma cells with the antibody-drug conjugate camidanlumab tesirine as a single agent or in combination with targeted agents
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Spriano, Filippo
ORCID
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Tarantelli, Chiara
ORCID
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Cascione, Luciano
ORCID
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
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Gaudio, Eugenio
ORCID
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Golino, Gaetanina
ORCID
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Scalise, Lorenzo
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Cacciapuoti, Maria Teresa
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, USA
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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
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Stathis, Anastasios
ORCID
Department of Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland - Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Van Berkel, Patrick H.
ADC Therapeutics (UK) Ltd., London, UK
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Inghirami, Giorgio
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York,USA
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Zammarchi, Francesca
ADC Therapeutics (UK) Ltd., London, UK
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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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Published in:
- British journal of haematology. - 2024, vol. 205, no. 5, p. 1873-1882
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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Medicine
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CC BY-NC-ND
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hybrid
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https://n2t.net/ark:/12658/srd1330221
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