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Abstract

AbstractAntibody humanizationRuuls et al., Biotechnol. J. 2008, 3, 1157–1171Monoclonal antibodies (mAbs) are increasingly used to treat human diseases, but as they are predominantly generated from mouse hybridomas their application has been hampered by their immunogenecity. To minimize antigenic reactions, researchers from Genmab in The Netherlands established a transgenic mouse platform for the routine production of fully humanized mAbs. In an overview of recent clinical research, the authors describe efficacy and mechanism of action of three novel humanized mAbs derived from this platform. Zanolimumab, Ofatumumab and Zalutumumab are designed to target CD4, CD20 and the epidermal growth factor receptor overexpressed on cancer cells and to attract cytotoxic reactions against them. All three humanized mAbs show improved efficacy in treatment trials of T‐cell lymphomas, B‐cell leukemias and head and neck cancer.Antibody productionZhou et al., Biotechnol. J. 2008, 3, 1185–1200Innovations in several aspects of antibody production technology have driven the commercialization of human therapeutic antibodies in recent years. As antibodies are complicated molecules that need several modes of secondary modification, like for example glycosylation and disulfide bonds, specific challenges have to be met. Moreover, one of the most important aims is to minimize production costs by increasing product throughput while maintaining product quality. Researchers from Amgen Inc (CA, USA) here review essential considerations and trends for commercial process development and optimization. One of the recent technical advances is the development and implementation of a disposable Q membrane adsorber. It is expected that production costs will be reduced dramatically at all levels of process development for largescale antibody production in the coming years.Antibody stabilityGaridel et al., Biotechnol. J. 2008, 3, 1201–1211Steady‐state intrinsic tryptophan fluorescence spectroscopy is used as a rapid, robust and economic way for screening the thermal protein conformational stability in various formulations used during the early biotechnology development phase. The most important parameters affecting protein stability in a liquid formulation, e.g. during the initial purification steps or preformulation development, are the pH of the solution, ionic strength, presence of excipients and combinations thereof. A well‐defined protocol is presented for the investigation of the thermal conformational stability of proteins. Researchers from Boehringer Ingelheim in Germany have now re‐evaluated and re‐assessed the influence of solution conditions on the emission spectra of tryptophan, phenylalanine and tyrosine. They show the advantage, challenges and applicability of using intrinsic tryptophan fluorescence spectroscopy as a routine development method in pharmaceutical biotechnology.