CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma

• Published in: Blood Vol. 122; no. 7; pp. 1233 - 1242
• Main Authors: Bhatt, Shruti, Ashlock, Brittany M., Natkunam, Yasodha, Sujoy, Victoria, Chapman, Jennifer Rose, Ramos, Juan Carlos, Mesri, Enrique A., Lossos, Izidore S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-08-2013; American Society of Hematology
• Subjects: Animals; Apoptosis - drug effects; Blotting, Western; Brentuximab Vedotin; Cell Cycle - drug effects; Cell Proliferation - drug effects; Flow Cytometry; Humans; Immunoconjugates - pharmacology; Ki-1 Antigen - immunology; Lymphoid Neoplasia; Lymphoma, Primary Effusion - immunology; Lymphoma, Primary Effusion - pathology; Lymphoma, Primary Effusion - prevention & control; Mice; Mice, Inbred NOD; Mice, SCID; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-01-481713

Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotin may serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients.
•Brentuximab vedotin serves as an effective therapy for PEL.•Brentuximab vedotin led to cytotoxic effects in PEL cell lines and extended survival of xenograft mice.