mAbs
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In a defining moment for the European Medicines Agency (EMA) and the biopharmaceutical industry, on June 27, 2013 EMA's Committee for Medicinal Products for Human Use adopted a positive opinion for two biosimilar infliximab products (Celltrion's Remsima® and Hospira's Inflectra®), and recommended that they be approved for marketing in the European Union (EU). The European Commission's decision on an application is typically issued 67 d after an opinion is provided; thus, decisions are expected in early September 2013. If approved, the products will comprise the first biosimilar antibody made available to patients in a highly regulated market, although launch may be delayed due to an extension of the reference product's (Remicade®) patent in the EU.
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Brentuximab vedotin (SGN-35; Adcetris®) is an anti-CD30 antibody conjugated via a protease-cleavable linker to the potent anti-microtubule agent monomethyl auristatin E (MMAE). Following binding to CD30, brentuximab vedotin is rapidly internalized and transported to lysosomes where MMAE is released and binds to tubulin, leading to cell cycle arrest and apoptosis. Several trials have shown durable antitumor activity with a manageable safety profile in patients with relapsed/refractory Hodgkin lymphoma, systemic anaplastic large cell lymphoma, or primary cutaneous CD30-positive lymphoproliferative disorders. ⋯ Neuropathy symptoms are cumulative and dose-related. Multiple ongoing trials are currently evaluating brentuximab vedotin alone or in combination with other agents in relapsed/refractory patients, as well as patients with newly diagnosed disease.
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Monoclonal antibodies are widely used for the treatment of cancer, inflammatory and infectious diseases and other disorders. Most of the marketed antibodies are monospecific and therefore capable of interacting and interfering with a single target. ⋯ This result can be achieved by combining different drugs, or use of the dual targeting strategies applying bispecific antibodies that have emerged as an alternative to combination therapy. This review discusses the various dual targeting strategies for which bispecific antibodies have been developed and provides an overview of the established bispecific antibody formats.
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Since their introduction, monoclonal antibodies have found an ever expanding role in the treatment of a wide number of disorders. However, the perturbation of the immune system that attends their use may also increase the risk for the development of disorders that arise in the setting of immunosuppressive conditions, such as, opportunistic infection and malignancy. In this paper, we address the association between some monoclonal antibodies and the development of a rare demyelinating disease of the brain, progressive multifocal leukoencephalopathy (PML). ⋯ Subsequently, efalizumab, a monoclonal antibody used in the treatment of psoriasis, was also demonstrated to be associated with PML. An increased risk has been suggested for rituximab, although most of the patients developing PML with that monoclonal antibody have been treated for B-cell disorders that predispose to the development of PML. Based on our current understanding of the biology of JC virus and the pathogenesis of PML, we propose an explanation for the increased risk for PML that is observed with natalizumab and certain other monoclonal antibodies.
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Asthma represents a syndrome of airway inflammatory diseases with complex pathology. The immunologic pathogenesis is being increasingly revealed and provides opportunity for targeted biological intervention. ⋯ Omalizumab is the only biological therapy that has an approved indication in asthma at this time. An improved understanding of the heterogeneity of asthma should allow for specific targeting of different disease phenotypes specific therapies including immunomodulators.