Anti-CD25 antibody–drug conjugates: improving the delivery of death to lymphoma cells?

In The Lancet Haematology, Mehdi Hamadani and colleagues 1 Hamadani M Collins GP Caimi PF et al. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol. 2021; 8: e433-e445 Summary Full Text Full Text PDF PubMed Scopus (14) Google Scholar report a large phase 1 study of the feasibility, safety, and activity of camidanlumab tesirine, an antibody–drug conjugate comprising a human anti-CD25 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer via a cleavable linker. After binding to CD25 present on lymphoma cells and normal activated B cells and T cells, camidanlumab tesirine enters the tumour cell by endocytosis, the linker is cleaved, and pyrrolobenzodiazepine causes death of the tumour cell via DNA cross-linking. Thus, camidanlumab tesirine represents another member of the rapidly increasing family of antibody–drug conjugates, the most prominent of which are brentuximab vedotin—licensed, among others, for first-line therapy and treatment of relapsed classical Hodgkin lymphoma and patients with CD30-positive anaplastic large cell lymphoma—and polatuzumab vedotin—licensed in combination with bendamustin and rituximab for patients with relapsed diffuse large B-cell lymphoma who are not eligible for transplantation. 2 Connors JM Jurczak W Straus DJ et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 2018; 378: 331-344 Crossref PubMed Scopus (395) Google Scholar , 3 Sehn LH Herrera AF Flowers CR et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020; 38: 155-165 Crossref PubMed Scopus (280) Google Scholar The high remission rates and favourable safety profiles reported suggest that treatment of haematological malignancies with antibody–drug conjugates represents a valid therapeutic principle and successful treatment option for patients with (relapsed) lymphoma in the real world. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion studyThese results warrant evaluation of camidanlumab tesirine as a potential treatment option for relapsed or refractory lymphoma, particularly in patients with classical Hodgkin lymphoma. Full-Text PDF