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

Introduction. Camidanlumab 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. Methods. Cell 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. Results. Camidanlumab tesirine presented much stronger single agent in vitro cytotoxic activity in T than B cell lymphomas. In vitro activity 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. Conclusion. The strong camidanlumab tesirine single agent anti-lymphoma activity and the observed in vitro synergisms with targeted agents support further clinical development of camidanlumab tesirine and identify potential combination partners for future clinical studies. ### Competing Interest Statement PHVB, FZ: ADC Therapeutics employees and stock owners. CT: travel grant from iOnctura. LC: travel grant from HTG Molecular Diagnostics. GG: currently, employee of Daiichi Sankyo Italia LS: currently, employee of SFL, a Veristat company. EZ: institutional research funds from Celgene, Roche, and Janssen; advisory board fees from Celgene, Roche, Mei Pharma, Astra Zeneca, and Celltrion Healthcare; travel grants from Abbvie and Gilead; and he has provided expert statements to Gilead, Bristol-Myers Squibb, and MSD AS: institutional research funds from Bayer, ImmunoGen, Merck, Pfizer, Novartis, Roche, MEI Pharma, and ADC-Therapeutics, and travel grants from AbbVie and PharmaMar. FB: institutional research funds from ADC Therapeutics, Bayer AG, Cellestia, Helsinn, HTG Molecular Diagnostics, ImmunoGen, iOnctura, Menarini Ricerche, NEOMED Therapeutics 1, Nordic Nanovector ASA, Sepxis AG; advisory board fees from Novarts; consultancy fee from Helsinn, Menarini; expert statements provided to HTG Molecular Diagnostics; travel grants from Amgen, Astra Zeneca, iOnctura. The other authors have no conflicts of interest.