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 (NHL) 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 (MMAE). Brentuximab vedotin is an effective treatment for 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 KSHV and EBV 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.
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ABSTRACT: Gene therapy is suggested to be one of the most specific and efficient modulations for gene deficient diseases and extended to other diseases like cancer and inflammation, even though there are still challenges to be faced, such as specific and selective delivery, minimal to no toxicity, efficient metabolism, simplicity, and measurable efficiency. It is important to identify and validate drug-able disease-specific targets for molecular and cellular therapies, while it is equally important to have disease biomarkers to trace and define the biological effects of molecular and cellular therapies. The importance and significance of allostery in molecular and cellular therapies and "allosteric disease", "allosteric effect", and "allosteric drug" should be more carefully examined and validated. Cell therapy has been attracting an increasing amount of consideration in the development of new treatments for diseases. Molecular and Cellular Therapies (MCT) is a new, open-access journal, devoted to molecular mechanisms, preclinical and clinical research and development of gene-, peptide-, protein-, and cell-based therapies.11/2013; 1(1):1. DOI:10.1186/2052-8426-1-1
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ABSTRACT: The association between viruses and lymphomas has long been recognized; however, the pathophysiological phenomena behind this relationship are unclear, and have been the object of intense research. Although our understanding of such mechanisms is slowly improving, much is still left to learn. With the recent advances in cancer biology, a diversity of biological pathways and novel targets and agents have been described in patients with haematological malignancies and successfully put into clinical practice. Clear examples are rituximab and brentuximab vedotin in patients with B cell lymphomas and Hodgkin lymphoma respectively. The main purpose of this review is not only to succinctly summarize what we know regarding the pathogenesis and pathophysiology of virally induced lymphomas and to describe the current practices in terms of diagnosis of treatment of such lymphomas, but also to provide a scientific rationale for the use of novel therapies that are likely to improve the outcomes of patients with these conditions.British Journal of Haematology 02/2014; 165(3). DOI:10.1111/bjh.12788 · 4.71 Impact Factor
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ABSTRACT: CD30 is an important therapeutic target for the treatment of malignant lymphomas. CD30 is a member of the TNF cell receptor superfamily and is highly expressed in a variety of lymphoma subsets, including Hodgkin lymphoma and anaplastic large cell lymphoma. Initial studies evaluated the safety and efficacy of several monoclonal antibodies targeting CD30, with limited success. More recently, the anti-CD30 drug-conjugate brentuximab vedotin produced high response rates with an excellent safety profile. These results lead to the approval of brentuximab vedotin for the treatment of patients with relapsed Hodgkin lymphoma and anaplastic large cell lymphoma. Current studies are focusing on incorporating brentuximab vedotin in front-line regimens and expanding its potential clinical utility in other CD30-expressing malignancies.Current Treatment Options in Oncology 02/2014; 15(2). DOI:10.1007/s11864-014-0275-7 · 3.24 Impact Factor