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Targeting CD25+ lymphoma cells with the antibody–drug conjugate camidanlumab tesirine as a single agent or in combination with targeted agents.
- Source :
-
British Journal of Haematology . Jul2024, p1. 10p. 5 Illustrations. - Publication Year :
- 2024
-
Abstract
- Summary 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANTIBODY-drug conjugates
*GENE expression
*CD25 antigen
*T-cell lymphoma
*LYMPHOMAS
Subjects
Details
- Language :
- English
- ISSN :
- 00071048
- Database :
- Academic Search Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 178713599
- Full Text :
- https://doi.org/10.1111/bjh.19658