With 18 monoclonal antibody (mAb) products currently on the market and more than 100 in clinical trials, it is clear that engineered antibodies have come of age as biopharmaceuticals. In fact, by 2008, engineered antibodies are predicted to account for >30% of all revenues in the biotechnology market. Smaller recombinant antibody fragments (for example, classic monovalent antibody fragments (Fab, scFv)) and engineered variants (diabodies, triabodies, minibodies and single-domain antibodies) are now emerging as credible alternatives. These fragments retain the targeting specificity of whole mAbs but can be produced more economically and possess other unique and superior properties for a range of diagnostic and therapeutic applications. Antibody fragments have been forged into multivalent and multispecific reagents, linked to therapeutic payloads (such as radionuclides, toxins, enzymes, liposomes and viruses) and engineered for enhanced therapeutic efficacy. Recently, single antibody domains have been engineered and selected as targeting reagents against hitherto immunosilent cavities in enzymes, receptors and infectious agents. Single-domain antibodies are anticipated to significantly expand the repertoire of antibody-based reagents against the vast range of novel biomarkers being discovered through proteomics. As this review aims to show, there is tremendous potential for all antibody fragments either as robust diagnostic reagents (for example in biosensors), or as nonimmunogenic in vivo biopharmaceuticals with superior biodistribution and blood clearance properties.

Engineered antibody fragments and the rise of single domains

Active targeting schemes for nanoparticle systems in cancer therapeutics.

Studies on anticancer activities of antimicrobial peptides.

Galectin-3: an open-ended story.

During the past decade, cancer stem cells (CSCs) have been increasingly identified in many malignancies Although the origin and plasticity of these cells remain controversial, tumour heterogeneity and the presence of small populations of cells with stem-like characteristics is established in most malignancies CSCs display many features of embryonic or tissue stem cells, and typically demonstrate persistent activation of one or more highly conserved signal transduction pathways involved in development and tissue homeostasis, including the Notch, Hedgehog (HH), and Wnt pathways CSCs generally have slow growth rates and are resistant to chemotherapy and/or radiotherapy Thus, new treatment strategies targeting these pathways to control stem-cell replication, survival and differentiation are under development Herein, we provide an update on the latest advances in the clinical development of such approaches, and discuss strategies for overcoming CSC-associated primary or acquired resistance to cancer treatment Given the crosstalk between the different embryonic developmental signalling pathways, as well as other pathways, designing clinical trials that target CSCs with rational combinations of agents to inhibit possible compensatory escape mechanisms could be of particular importance We also share our views on the future directions for targeting CSCs to advance the clinical development of these classes of agents

Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update

GlycoExpress : A novel express for the optimal glycosylation of biotherapeutics

The present invention pertains to the field of recombinant protein production. Novel peptides derived from the extracellular region of a glycophorin protein are provided which enhance the expression rate of proteins or peptides of interest when expressed as fusion protein together with said novel peptides.

Peptides for enhancing protein expression

The present invention pertains to IgA antibodies having an optimized glycosylation pattern. These IgA antibodies exhibit an increased stability and an extended shelf life. Compositions comprising IgA antibodies having an improved glycosylation pattern and methods for improving the shelf life of IgA antibodies are provided.

Iga antibodies with enhanced stability

The present invention pertains to food products comprising microorganisms of the species Bacteroides xylanisolvens, in particular fermented food and probiotic food. These microorganisms are particularly characterized as having a very low pathogenicity and a high safety for human consumption.Furthermore, methods for producing said food products, in particular by fermentation, as well as suitable bacterial strains Bacteroides xylanisolvens of are provided.

Microorganisms of the species bacteroides xylanisolvens

The invention relates to a method for the isolation of large variances of specific molecules for a target molecule from phagemid gene libraries and to a test kit, said method being performed by starting with a phagemid gene library including large variances of a molecule or large variances of portions of a molecule which, in the meaning of the invention, acts as a specific molecule, directly, or via a linker, coupled covalently to the phage coat protein pIII of the filamentous phage M 13 as a fusion protein on the surface of phages, incubating the library phages including the phages expressing the fusion protein with a target molecule, eluting the phages specifically bound to the target molecule via the fusion protein with a selection molecule which terminates binding between the specific molecule and the target molecule and binds to the target molecule, inactivating the eluted phages failing to express the fusion protein in a way so as to render them incapable of infecting bacteria, using the eluted phages expressing the fusion protein to infect bacteria, and determining and obtaining the variances of the specific molecule from the infected clones.

Steffen Goletz

Papers

GlycoExpress : A novel express for the optimal glycosylation of biotherapeutics

Peptides for enhancing protein expression

Iga antibodies with enhanced stability

Microorganisms of the species bacteroides xylanisolvens

Method for the isolation of large variances of specific molecules for a target molecule from phagemid gene libraries, and a test kit