In a study presented in PLoS ONE, Pål K. Selbo from the Department of Radiation Biology (Kristian Berg’s group) and co-workers describe for the first time the use of photochemical internalization (PCI) as a modality to enhance the delivery of a tumour-targeting drug in vivo.
The article - entitled "Multi-Modality Therapeutics With Potent Anti-Tumor Effects: Photochemical Internalization Enhances Delivery of the Fusion Toxin scFvMEL/rGel" is a result of collaboration with researchers at the M.D. Anderson Cancer Center, Houston, Texas.
PCI is a specific drug delivery system which release entrapped drugs in intracellular vesicles such as endosomes and lysosomes. The technology is based on the light-activation of dyes/photosensitizers followed by the formation of reactive oxygen species which burst the vesicles and release the drug of interest in the targeted cancer cells.
PCI was found to induce cytosolic release and dramatically enhance in vitro cytotoxicity of a recombinant fusion toxin, scFvMEL/rGel, which targets the HMW-MAA/NG2 antigen that is expressed in the majority of malignant melanomas, lobular breast carcinomas and adult and childhood brain tumours. PCI strongly enhanced the anti-tumour effect of the recombinant fusion construct while no adverse side effects were observed in nude mice. The model xenograft used was a non-pigmented human melanoma transplanted subcutaneously on the hip of nude mice. PCI resulted in complete response in 33% of the laser-exposed mice while only a weak growth arrest for a few days were obtained in the control mice.
Several years ago, Pål K. Selbo established a collaboration with Professor Michael Rosenblum in the Department of Experimental Therapeutics, M.D. Anderson Cancer Center in Houston, Texas. In 2009, MDACC was ranked as the number 1 Cancer Center among US specialty Hospitals by US News and World Reports.
Quote from the paper: "The present study demonstrates for the first time the tumor-targeting potential of PCI as a novel modality which may be deployed in combination with other targeted therapeutic agents. PCI of fusion toxins is a promising and innovative non-invasive, in situ treatment of cancer. Lower drug doses used to achieve anti-cancer effects made possible by the PCI technology might lead to significant reduction of drug or treatment-induced adverse events in humans".
Paper in PLoS ONE:
Multi-Modality Therapeutics With Potent Anti-Tumor Effects: Photochemical Internalization Enhances Delivery of the Fusion Toxin scFvMEL/rGel
Pål K. Selbo, Michael G. Rosenblum, Lawrence H. Cheung, Wendy Zhang, Kristian Berg
PLoS ONE 2009 Aug 19