Biopharmaceutical drug discovery using novel protein scaffolds

Gill, Davinder; Damle, Nitin K.

doi:10.1016/j.copbio.2006.10.003

Cited by 60 publications

(26 citation statements)

References 20 publications

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“…The variable heavy domain of these hcAbs (V HH ) can be subjected to humanization and thus used for the development of so called nanobodies (Nb) [109]. In addition, single domains can be selected by exploring various protein scaffolds, which have been established as antibody mimetics [110,111]. Due to their simple structure sdAbs and antibody mimetics are very easy to manipulate, engineer and produce.…”

Section: Evolution Of Bispecific Antibodiesmentioning

confidence: 99%

Cancer Immunotherapy by Retargeting of Immune Effector Cells via Recombinant Bispecific Antibody Constructs

Stamova¹,

Koristka²,

Keil³

et al. 2012

Antibodies

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Immunotherapy has emerged as an alternative strategy to treat malignancies in addition to conventional radio- and chemotherapy. There has been a plethora of evidence that the immune system is able to control tumor outgrowth and a number of strategies have been put forward to utilize this ability for immunotherapy. However, some of these strategies have not been very efficient and their success has been limited by tumor evasion mechanisms. A promising approach to engage effector cells of the immune system overcoming some of the escape mechanisms has been introduced more than two decades ago. This approach is based on bispecific antibodies. Here we summarize the evolution of bispecific antibodies, their improvement, remaining obstacles and some controversial reports.

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Section: Evolution Of Bispecific Antibodiesmentioning

confidence: 99%

Cancer Immunotherapy by Retargeting of Immune Effector Cells via Recombinant Bispecific Antibody Constructs

Stamova¹,

Koristka²,

Keil³

et al. 2012

Antibodies

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“…Specific binding proteins, e.g., antibodies, are becoming increasingly important in almost all areas of life science, from large-scale proteome projects (47,49) to in vivo imaging (26,31,34,50) and biotherapy (1,10). To meet the increasing demands, much effort has been put into developing and improving different methods for the generation of such binders.…”

mentioning

confidence: 99%

Evaluation of Staphylococcal Cell Surface Display and Flow Cytometry for Postselectional Characterization of Affinity Proteins in Combinatorial Protein Engineering Applications

Löfblom

Sandberg

Wernérus

et al. 2007

Appl Environ Microbiol

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For efficient generation of high-affinity protein-based binding molecules, fast and reliable downstream characterization platforms are needed. In this work, we have explored the use of staphylococcal cell surface display together with flow cytometry for affinity characterization of candidate affibody molecules directly on the cell surface. A model system comprising three closely related affibody molecules with different affinities for immunoglobulin G and an albumin binding domain with affinity for human serum albumin was used to investigate advantages and differences compared to biosensor technology in a side-by-side manner. Equilibrium dissociation constant (K D ) determinations as well as dissociation rate analysis were performed using both methods, and the results show that the on-cell determinations give both K D and dissociation rate values in a very fast and reproducible manner and that the relative affinities are very similar to the biosensor results. Interestingly, the results also show that there are differences between the absolute affinities determined with the two different technologies, and possible explanations for this are discussed. This work demonstrates the advantages of cell surface display for directed evolution of affinity proteins in terms of fast postselectional, on-cell characterization of candidate clones without the need for subcloning and subsequent protein expression and purification but also demonstrates that it is important to be aware that absolute affinities determined using different methods often vary substantially and that such comparisons therefore could be difficult.

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“…Without doubt, the idea of applying antibody surrogates for practical use has been generally accepted by now, as illustrated by the fact that several protein scaffolds are already pursued for medical applications [5,18]. It seems, however, that the field of protein scaffold engineering is approaching a stage of saturation with regard to the repertoire of architectures that are being considered.…”

Section: The 'Scaffold' Idea: Evolution and Consolidationmentioning

confidence: 97%