Institute seminar January 27th 10.30 Kristian Berg

From bench to bedside with a novel technology for site-specific drug delivery

Abstract

The utilisation of macromolecules in therapy of cancer and other diseases is becoming increasingly important. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. To achieve the expected biological effect of these macromolecules in many cases internalisation to the cell cytosol is crucial. At an intracellular level, the most fundamental obstruction for cytosolic delivery of therapeutic macromolecule is the membrane-barrier of the endocytic vesicles. Photochemical internalisation (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. The technology is based on the use of photosensitizers located in endocytic vesicles that upon activation by light induces rupture of the endocytic vesicles and thereby release of the macromolecules into the cytosol. PCI has been shown to enhance the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus, oligonucleotides and the chemotherapeutic agent bleomycin. PCI has also been shown to enhance the treatment effect of targeted therapeutic macromolecules. The results indicate that PCI may have a variety of useful applications for site-specific drug delivery, e.g. in gene therapy, vaccination and cancer treatment. The basic mechanisms of action, some examples of the efficacy and specificity as well as the initial results from an ongoing phase I/II clinical PCI-trial will be presented.

Links:

Kristian Berg's group - Photochemical Internalisation (PCI)

Department of Radiation Biology

Institute seminar list, spring semester 2010