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Monoclonal and bispecific antibodies as novel therapeutics

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Booy E. P., Johar D., Maddika S., Pirzada H., Sahib M. M., Gehrke I., Loewen S., Louis S. F., Kadkhoda K., Mowat M., Los M.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 2
85-101
EN
Gene amplification, over-expression, and mutation of growth factors, or the receptors themselves, causes increased signaling through receptor kinases, which has been implicated in many human cancers and is associated with poor prognosis. Tumor growth has been shown to be decreased by interrupting this process of extensive growth factor-mediated signaling by directly targeting either the surface receptor or the ligand and thereby preventing cell survival and promoting apoptosis. Monoclonal antibodies have long been eyed as a potential new class of therapeutics targeting cancer and other diseases. Antibody-based therapy initially entered clinical practice when trastuzumab/Herceptin became the first clinically approved drug against an oncogene product as a well-established blocking reagent for tumors with hyperactivity of epidermal growth factor signaling pathways. In the first part of this review we explain basic terms related to the development of antibody-based drugs, give a brief historic perspective of the field, and also touch on topics such as the 'humanization of antibodies' or creation of hybrid antibodies. The second part of the review gives an overview of the clinical usage of bispecific antibodies and antibodies 'armed' with cytotoxic agents or enzymes. Further within this section, cancer-specific, site-specific, or signaling pathway-specific therapies are discussed in detail. Among other antibody-based therapeutic products, we discuss: Avastin (bevacizumab), CG76030, Theragyn (pemtumomab), daclizumab (Zenapax), TriAb, MDX-210, Herceptin (trastuzumab), panitumumab (ABX-EGF), mastuzimab (EMD-72000), Erbitux (certuximab, IMC225), Panorex (edrecolomab), STI571, CeaVac, Campath (alemtuizumab), Mylotarg (gemtuzumab, ozogamicin), and many others. The end of the review deliberates upon potential problems associated with cancer immunotherapy.
2

Uses of monoclonal antibodies in medicine

100%
Zielinski M., Plucienniczak A.
Biotechnologia
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2009
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issue 2
113-122
EN
This review article describes uses of monoclonal antibodies (mAb) in medicine as therapeutics. It contains information about the method of monoclonal antibodies production, types of their modifications and nomenclature. We show examples of mAb application in therapies.
3

RNA interference:a potential novel therapeutic combating HIV-1 in the central nervous system

100%
Pomerantz R. J.
Archivum Immunologiae et Therapiae Experimentalis
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2004
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vol. 52
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issue 6
401-409
EN
RNA interference (RNAi) is a conserved process by which eukaryotic cells protect their genomes utilizing small, double-stranded RNAs to degrade target RNAs. This occurs in a sequence-specific manner and is different from the interferon effect of larger doublestranded RNAs. Post-transcriptional gene silencing by these nucleic acids can lead to degradation of either cellular or viral RNAs. It has been recently shown that doublestranded, small interfering RNAs (siRNAs) of 21 to 25 nucleotides can be transfected into relevant cells to target specific RNAs. In addition, utilizing hairpin motifs, siRNAs can be expressed intracellularly using molecular therapeutic vectors. This potent approach has been utilized to both inhibit pathogens, including viruses, as well as to dissect cellular molecular mechanisms via a potent knockout effect. At this time in the HIV-1-pandemic, one of the remaining, most enigmatic, and still vitally important areas of HIV-1 pathogenesis occurs in the central nervous system (CNS). HIV-1-induced encephalopathy remains difficult to treat in the developing world and in parts of the developed world, even in the era of highly active anti-retroviral therapy. As such, novel approaches which could lead to intracellular immunization, and life-long resistance against HIV-1 encephalopathy would be of important impact worldwide. Thus, we now seek to combine our background in molecular therapeutics and RNAi with our long-standing interest in HIV-1 neuropathogenesis to target the CNS using siRNAs.
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