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

Abstract

ABSTRACTIntroductionCamidanlumab tesirine (ADCT-301) is a CD25 specific antibody-drug conjugate (ADC) employing SG3199, a highly cytotoxic DNA minor groove cross-linking pyrrolobenzodiazepine dimer. Camidanlumab tesirine has shown early clinical anti-tumor activity in various cancer types, including B- and T-cell lymphomas. Here, we assessed its preclinical activity as single agent in 57 lymphoma cell lines and in combination with selected drugs in T cell lymphomas-derived cell lines.MethodsCell lines were exposed to increasing concentrations of camidanlumab tesirine or to SG3199 for 96h followed by MTT proliferation assay. CD25 expression was measured both at cell surface level via fluorescence quantitation and at RNA level, using various technologies. Combination studies were performed exposing cells to increasing doses of camidanlumab tesirine and of additional drugs.ResultsCamidanlumab tesirine presented much stronger single agentin vitrocytotoxic activity in T than B cell lymphomas.In vitroactivity was highly correlated with CD25 expression both at cell surface level and RNA level. Based on the higher activity in T cell lymphomas, camidanlumab tesirine-containing combinations were evaluated in cell lines derived from peripheral T cell lymphoma, ALK-pos or ALK-neg anaplastic large cell lymphoma. The most active combination partners were everolimus, copanlisib, venetoclax, vorinostat and pralatrexate, followed by bortezomib, romidepsin, bendamustine and 5-azacytidine.ConclusionThe strong camidanlumab tesirine single agent anti-lymphoma activity and the observedin vitrosynergisms with targeted agents support further clinical development of camidanlumab tesirine and identify potential combination partners for future clinical studies.