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Contenido archivado el 2024-04-30

Regional transfer and optimisation of technology related to identification and production of antibody specificities using phage display libraries

Objetivo

The standard method for generating specific antibodies is immunisation of animals with the relevant antigen, followed by selection and immortalisation of single lymphocyte clones by fusion to a myeloma cell line. Over the last two decades this method has been extremely valuable for the development of a wide range of biomedical products. However, its dependence on in vivo immunisation represents some major limitations for molecular targets with poor immunogenicity, such as haptens or self-antigens. Moreover, as the resulting antibodies are of murine origin, they are in most cases unsuitable for therapeutic purposes.

The selection of recombinant antibodies in vitro from phage display libraries is a novel alternative, which circumvents most of these problems and provides access to a multitude of antibodies with novel specificites. This technology has been developed in parallel by a number of European and American laboratories, including the German Cancer Research Centre in Heidelberg.

The main objective of this project was to combine the antibody library technology with state of the art methods for biomagnetic separation. The Norwegian company Dynal AS has proprietary technology for the production of monodisperse paramagnetic beads, and has exploited this extensively for solid phase separation in biomedicine. Biomagnetic separation is expected to provide significant improvements during several steps of the antibody selection process. This included preparation of cell surface antigens and immobilisation of antigen during biopanning. The project planned to optimise the bead technology for these purposes leading to a versitile tool for antibody selection. Two national centres for cancer research (NRH, Oslo and DKFZZ, Heidelberg) contributed to the search for antibodies against tumour markers, which will then be evaluated for their diagnostic potential.

Another major outcome of the project was to optimise the surface of the paramagnetic beads with respect to immobilisation of recombinant antibodies obtained from the libraries. Depending on the particular antibody specificity, this will create a general system for immunopurification of cells, proteins or small molecular compounds from complex biological samples.

Finally, this project sought to provide valuable support for a newly established firm in Oslo (Affitech AS), which concentrates on immune based products developed directly by the antibody library technology. Transferred know-how for library generation and selection was initially used to develop antibodies against certain small molecular compounds with relevance for public health surveillance. More recently Affitech has used the technology to establish a pipeline of projects aiming for new antibody-based medicines, alone, and in collaboration with commercial and academic partners.

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Coordinador

AFFITECH AS
Aportación de la UE
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