title: CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Bhatt
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Ashlock
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Victoria
authors.initials: V
authors.lastname: Sujoy
authors.forename: Jennifer Rose
authors.initials: JR
authors.lastname: Chapman
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramos
authors.forename: Enrique A
authors.initials: EA
authors.lastname: Mesri
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D000079963:Brentuximab Vedotin; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D017730:Ki-1 Antigen / Q000276:immunology*; D054685:Lymphoma, Primary Effusion / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D018796:Immunoconjugates; D017730:Ki-1 Antigen; D012333:RNA, Messenger; D000079963:Brentuximab Vedotin