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

Spriano, Filippo; Tarantelli, Chiara; Cascione, Luciano; Gaudio, Eugenio; Golino, Gaetanina; Scalise, Lorenzo; Cacciapuoti, Maria Teresa; Zucca, Emanuele; Stathis, Anastasios; Van Berkel, Patrick H.; Inghirami, Giorgio; Zammarchi, Francesca; Bertoni, Francesco

doi:10.1111/bjh.19658

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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

2024

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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