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Selected technologies to control genes and their products for experimental and clinical purposes

100%

Alexander H. K., Booy E. P., Xiao W., Ezzati P., Baust H., Los M.

2007

vol. 55

issue 3

139-149

'On-demand' regulation of gene expression is a powerful tool to elucidate the functions of proteins and biologically-active RNAs. We describe here three different approaches to the regulation of expression or activity of genes or proteins. Promoter-based regulation of gene expression was among the most rapidly developing techniques in the 1980s and 1990s. Here we provide basic information and also some characteristics of the metallothionein-promoter-based system, the tet-off system, Muristerone-A-regulated expression through the ecdysone response element, RheoSwitch?, coumermycin/novobiocin-regulated gene expression, chemical dimerizer-based promoter activation systems, the 'Dual Drug Control' system, 'constitutive androstane receptor'-based regulation of gene expression, and RU486/mifepristone-driven regulation of promoter activity. A large part of the review concentrates on the principles and usage of various RNA interference techniques (RNAi: siRNA, shRNA, and miRNA-based methods). Finally, the last part of the review deals with historically the oldest, but still widely used, methods of temperature-dependent regulation of enzymatic activity or protein stability (temperature-sensitive mutants). Due to space limitations we do not describe in detail but just mention the tet-regulated systems and also fusion-protein-based regulation of protein activity, such as estrogen-receptor fusion proteins. The information provided below is aimed to assist researchers in choosing the most appropriate method for the planned development of experimental systems with regulated expression or activity of studied proteins.

Monoclonal and bispecific antibodies as novel therapeutics

68%

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

2006

vol. 54

issue 2

85-101

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.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 2007

1 2006

2 Booy E. P.

2 Los M.

1 Alexander H. K.

1 Baust H.

1 Ezzati P.

1 Gehrke I.

1 Johar D.

1 Kadkhoda K.

1 Loewen S.

1 Louis S. F.

1 Maddika S.

1 Mowat M.

1 Pirzada H.

1 Sahib M. M.

1 Xiao W.

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Selected technologies to control genes and their products for experimental and clinical purposes

Monoclonal and bispecific antibodies as novel therapeutics