Advances in antibody-based therapy in oncology.

Monoclonal antibodies are a growing class of targeted cancer therapeutics, characterized by exquisite specificity, long serum half-life, high affinity and immune effector functions. In this review, we outline key advances in the field with a particular focus on recent and emerging classes of engineered antibody therapeutic candidates, discuss molecular structure and mechanisms of action and provide updates on clinical development and practice.

Transient expression of human antibodies in mammalian cells.

Recombinant expression of antibody molecules in mammalian cells offers important advantages over traditionally utilized bacterial expression, including glycosylation required for antibody functionality and markedly reduced levels of endotoxin contamination. Advances in transient mammalian expression systems enable high yields (>100 mg/liter) that now allow for effective recombinant antibody production at a reasonable cost. Here, we provide step-by-step protocols for the design and recombinant expression of full-length IgG antibodies and antibody-derived constructs (including Fab, Fc-fusions and bispecifics) in mammalian cells. Antibody constructs are designed by combining antibody variable domains, generated by phage display or derived from human/humanized monoclonals, with constant regions. The constructs are then expressed from mammalian vectors, secreted into culture media, purified by affinity chromatography and characterized by biolayer interferometry. This article provides detailed protocols, sequences and strategies that allow the expression and purification of endotoxin-free antibody reagents suitable for testing in animal models within a 3-week time frame.

Challenges and opportunities for non-antibody scaffold drugs.

The first candidates from the promising class of small non-antibody protein scaffolds are now moving into clinical development and practice. Challenges remain, and scaffolds will need to be further tailored toward applications where they provide real advantages over established therapeutics to succeed in a rapidly evolving drug development landscape.

Thermal comfort range of a military cold protection glove: database by thermophysiological simulation.

The thermal insulation properties of a military wet/cold protection glove of the German Bundeswehr were investigated using the thermophysiological simulation device CYBOR with a heated full-scale hand model. The aim of this study was the physiology related and more reliable estimation of a database for the thermal comfort range of the glove in terms of environmental limit temperatures and maximum safe wearing times (limit times). For that purpose the simulation device CYBOR is equipped with a control feature allowing the simulation of the physiological effect that the blood flow into the hands as the dominant heat source is reduced with decreasing skin temperature (vasoconstriction effect). In the simulation test, the criterion defining the thermal comfort range of the glove was the maintenance of a minimum hand phantom skin temperature of 15 degrees C. For various assumed metabolic rates between 50 and 175 W m(-2) and environmental temperatures down to -22 degrees C, the maximum safe wearing times within the thermal comfort range of the military glove were estimated between only 20 min and almost 1 h. The used simulation scenario for the prediction of environmental limit temperatures, however, tends to deliver too low values in correlation to the estimated limit times and needs further critical consideration. The estimated data concerning the thermal comfort range of the wet/cold protection glove of the German Bundeswehr leads to the recommendation for a use of this model in mild cold climatic regions. The presented thermophysiological simulation procedure for the evaluation of the cold protection properties of gloves in terms of maximum safe wearing times within the thermal comfort range can be a useful tool to establish practical operating instructions for soldiers or civilians acting in cold environments.