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Adenovirus Infection Enhances Killing of Melanoma Cells by a Mitotoxin¹

The Wistar Institute, Philadelphia, Pennsylvania 19104

Toxins are effective in cell killing if internalized efficiently. Conjugation of the plant toxin saporin with basic fibroblast growth factor has increased tumor killing due to better internalization, but toxin uptake by cells has remained relatively inefficient. We show here that infection of melanoma cells with a replication-defective adenovirus enhances cell killing by the mitotoxin basic fibroblast growth factor-saporin more than 10-fold, thus allowing tumor cell killing in vivo at nontoxic concentrations. Adenovirus infection leads to increased apoptosis by the mitotoxin due to enhanced internalization of the ligand-receptor complex and release of the active toxin from the endosomes.

¹ Supported by NIH Grants CA 25874 and CA 47159 and the Cancer Center Core Grant CA 10815.

² To whom requests for reprints should be addressed, at The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104. Phone: (215) 898-3950; Fax: (215) 898-0980; E-mail: herlynm@wista.wistar.upenn.edu.

Received 3/ 7/97. Accepted 4/ 2/97.

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