Department of Biotechnology
Molecular Biotechnology
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  Biotherapy and Bacterial Display
Summary
Eriksson Karlström
Gräslund
Nygren
Samuelson
Ståhl

Principal Investigator (PI): Prof Stefan Ståhl

Personnel:
PhD-students: Tarek Bass, Filippa Fleetwood, Hanna Lindberg, Magdalena Malm, Lisa Sandersjöö
PostDocs: Andreas Jonsson, Ronny Falk, Helena Wållberg
Assistant Professor: John Löfblom

Description of present activities:
Affibody-mediated biotherapy: A novel class of affinity proteins, denoted affibody ligands, has been developed at our department. Affibody molecules are based on a 58-amino acid residue protein domain, derived from staphylococcal protein A, which has served as scaffold for construction of combinatorial libraries from which affibody binding proteins can be selected to desired target proteins. In this project, their potential in various therapeutic settings are investigated, including tumor targeting for in vivo imaging and radiotherapy applications. Cancer biomarkers such as HER2, EGFR and HER3 have been used in the context of tumor targeting, and mono- bi- and multispecific formats are being investigated. In addition, the amyloid beta peptide of Alzheimer’s disease have been used as target for selection of affibody molecules which are subject to preclinical investigations for the prevention of plaque formation.
Staphylococcal surface display: The group has during the last 15 years developed novel host vector systems for efficient surface display on food grade staphylococci, e.g. Staphylococcus carnosus, and used these surface display systems successfully for subunit vaccine delivery, or as whole cell tools for diagnostic or environmental applications. The present focus is to evaluate staphylococci for protein library applications using fluorescence activated cell sorting (FACS) for library screening. The system is presently evaluated for selection of affinity proteins, i.e. affibody molecules and domain antibodies, using surface-displayed libraries, as well as for epitope mapping of polyclonal and monoclonal antibodies.
Ten recent publications:

1.

Altai, M., Wållberg, H., Orlova, A., Rosestedt, M., Hosseinimehr, S.J., Tolmachev, V. and Ståhl, S. Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of 99mTc-labeled recombinant affibody molecules. Amino Acids (2012) In Press. IF 4.1

2.

Löfblom, J., Frejd, F.Y. and Ståhl, S. Non-immunoglobulin based protein scaffolds. Curr. Opin. Biotechnol. 22: 843-848 (2011). IF 8.5

3.

Wållberg, H., Orlova, A., Altai, M., Jalal Hosseinimehr, S., Widström, C., Malmberg, J., Ståhl, S. and Tolmachev, V. Molecular design and optimization of 99mTc-labeled recombinant affibody molecules improves their biodistribution and imaging properties. J. Nuclear Med. 52: 461-469 (2011). IF 5.9

4.

Luheshi, L.M., Hoyer, W., de Barros, T.P., van Dijk Härd, I., Brorsson, A.C., Macao, B., Persson, C., Crowther, D.C., Lomas, D.A., Ståhl, S., Dobson, C.M. and Härd, T. Sequestration of the Aß peptide prevents toxicity and promotes degradation in vivo. PLoS Biology 8: e1000334 (2010). IF 12.9

5.

Löfblom, J., Feldwisch, J., Tolmachev, V., Carlsson, J., Ståhl, S. and Frejd, F.Y. Affibody molecules: Engineered proteins for therapeutic, diagnostic and biotechnological applications. FEBS Letters 584: 2670-2680 (2010). I.F. 3.6

6.

Myhre, S., Magnusson, M.K., Henning, P., Friedman, M., Ståhl., S., and Lindholm, L. Re-targeted Adenovirus vectors with dual specificity; binding specificities conferred by two different Affibody molecules in the fiber. Gene Therapy 16: 252-261 (2009) I.F. 4.8.

7.

Friedman, M., Orlova, A., Johansson, E., Eriksson, T., Höidén-Guthenberg, I., Nilsson, F.Y., Tolmachev, V. and Ståhl, S. Directed evolution to low nanomolar affinity of a tumor-targeting epidermal growth factor receptor-binding Affibody molecule. J. Mol. Biol. 376: 1388-1402 (2008). I.F. 4.5

8.

Tolmachev, V., Friedman, M., Sandström, M., Eriksson, T., Rosik, D., Hodik, M., Ståhl, S., Nilsson, F.Y. and Orlova, A. Affibody molecules for epidermal growth factor receptor targeting in vivo: aspects of dimerization and labeling chemistry. J. Nuclear Med. 50: 274-283 (2009) I.F. 5.9

9.

Hoyer, W., Grönwall, C., Jonsson, A., Ståhl, S. and Härd, T. Stabilization of a ß-hairpin in monomeric Alzheimer’s amyloid-ß peptide inhibits amyloid formation. Proc. Natl. Acad. Sci. USA 105: 5099-5104 (2008). I.F. 9.8.

10.

Rockberg, J./Löfblom, J., Hjelm, B., Uhlén, M., and Ståhl, S. Combinatorial epitope mapping of antibodies using staphylococcal surface display. Nature Methods 5: 1037-1045 (2008) . I.F. 20.7

Last updated: 2012-06-13