Photochemical internalisation increases the cytotoxic effect of the immunotoxin MOC31-gelonin

Photochemical internalisation (PCI) was recently demonstrated as a unique p rocedure for site-specific delivery of several types of membrane Impermeabl e macromolecules from endocytotic vesicles to the cytosol (Berg et ol,, 199 9), The technology is based on the cytosolic release of endocytosed macromo lecules from endosomes and lysosomes upon exposure of cells to photosensiti sing compounds, which became localised to these vesicles, and light, In our study the possibility to increase the cytotoxic effect of the immunotoxin MOC31-gelonin by PCI was examined. The type I ribosome-inactivating protein gelonin was covalently linked to the monoclonal IgG1 antibody MOC31, direc ted against epithelial glycoprotein-2 (EGP-2), an antigen expressed on most carcinoma cells. Five different cell lines, of which 4 expressed EGP-2, we re treated with MOC31-gelonin and endosomal and lysosomal localising photos ensitisers, followed by exposure to light. Insignificant cytotoxicity of th e MOC31-gelonin was observed when the cells were incubated with the immunot oxin alone. However, in combination with endosomal and lysosomal localising photosensitizers, we demonstrate synergistic toxic effect of the MOC31-gel onin conjugate in a light-dependent manner. Our results indicate that PCI i s a promising tool for increasing the cytotoxicity of immunotoxins, which i s important for further improvement of the PCI concept towards possible use in cancer therapy. Int. J. Cancer 87:853-859, 2000, (C) 2000 Wiley-Liss, I nc.