Molecular Biotechnology Programme
Uppsala University School of Engineering
UPTEC X 11 023 Date of issue 2011-04 Author
Erika von Hage
Title (English)
Functional characterisation in vitro of an Affibody® molecule aimed for vascular targeted tumour therapy
Title (Swedish) Abstract
In a certain type of cancer immunotherapy, IL-2 is administered in high doses to the patient in order to trigger an immune response against tumour cells. The high dose administered leads to high general toxicity. By targeting IL-2 to the sites of the tumours, the dose can be decreased and toxicity reduced. Here, a PDGFR-! specific fusion protein (Z03358-ABD-IL2) aimed for delivery of IL-2 to tumour vasculature, has been characterised in vitro for IL-2-activity and target binding. Also, two PDGFR-! specific Affibody molecules (Z02465 and Z02483) have been characterised in vitro for target binding and biological blocking activity. Results showed that Z03358-ABD-IL2 had full IL-2 activity, but decreased target binding. In contrast, full target binding and blocking capacity was confirmed with Z02465 and Z02483. From this work it can be concluded that Z03358-ABD-IL2 has activity in all parts, but re-cloning with Z02465 or Z02483 should be considered for full target binding capacity.
Keywords
Cancer, tumour vasculature, tumour targeting, IL-2, Affibody molecule, pericyte, PDGFR-!
Supervisors
Fredrik Frejd & Ingmarie Höidén-Guthenberg Affibody AB
Scientific reviewer
Angelica Loskog Uppsala universitet
Project name Sponsors
Language
English Security
ISSN 1401-2138 Classification
Supplementary bibliographical information Pages
36
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