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

La presente invention concerne des anticorps anti-EGFR humanises presentant des proprietes de liaison antigenique semblables a celles de l'anticorps anti-EGFR murin ou chimerique dont ils sont derives. En particulier, la presente invention concerne des anticorps anti-EGFR humanises qui sont utiles dans le traitement du cancer.

Anticorps anti-egfr humanisés

L'invention concerne des molecules de reconnaissance dirigees contre les tumeurs, les compositions pharmaceutiques contenant ces molecules de reconnaissance, des procedes de production de ces molecules de reconnaissance et l'utilisation de ces dernieres pour le diagnostic et la therapie de maladies tumorales.

Molecules de reconnaissance pour le traitement et la detection de tumeurs

The present invention pertains to methods for producing a γ-carboxylated polypeptide by a host cell having γ-glutamyl carboxylase activity. The production is improved by the presence of vitamin K and cyclodextrin in the cell culture medium.

IMPROVED METHOD FOR PRODUCTION OF γ-CARBOXYLATED POLYPEPTIDES

Utilisation des cellules humaines provenant d'une leucémie myéloïde pour l'expression d'anticorps

La presente invention concerne des glycoproteines extremement actives presentant des degres de sialylation specifiques, une composition pharmaceutique utilisee dans un diagnostic ou une therapie impliquant lesdites glycoproteines, une methode servant a determiner des glycoproteines extremement actives et les conditions de leur production, et une methode de sialylation differentielle de glycoproteines secretrices. Ladite invention a aussi trait a l'utilisation de glycoproteines extremement actives exprimees de maniere recombinante utilisees a des fins biologiques et dans le traitement ou le diagnostic prophylactique et/ou therapeutique de maladies, notamment, lors d'une transplantation de moelle osseuse, de neutropenie, de cytopenie, de leucemie myeloide grave et de syndromes myelodysplasiques, de cancer, du VIH et/ou de maladies de systemes hematopoietiques.

Steffen Goletz

Papers

Anticorps anti-egfr humanisés

Molecules de reconnaissance pour le traitement et la detection de tumeurs

IMPROVED METHOD FOR PRODUCTION OF γ-CARBOXYLATED POLYPEPTIDES

Utilisation des cellules humaines provenant d'une leucémie myéloïde pour l'expression d'anticorps

Conditions de traitement de glycoproteines extremement actives et methode efficace de production associee