Cytotoxicity of gelonin conjugated to targeting molecules: effects of weak amines, monensin, adenovirus, and adenoviral capsid proteins penton, hexon, and fiber

VS Goldmacher, WA Blattler, JM Lambert, G McIntyre and J Stewart

Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.

It has been reported previously that ammonium chloride, chloroquine, monensin, and adenovirus-2 potentiate the cytotoxicity of several protein toxins conjugated with various targeting molecules. We have tested whether these agents, and protein components of adenovirus-2, would enhance the cytotoxicity of conjugates of gelonin with J5, an antibody directed against common acute lymphoblastic leukemia- associated antigen, with 5E9, an antibody directed against human transferrin receptor, or with ricin B-chain. We found that none of these agents affected the cytotoxicity of gelonin conjugates to any significant extent. For example, monensin moderately (3-fold) enhanced the cytotoxicity of 5E9-gelonin for Namalwa cells but showed no effect when 5E9-gelonin was tested on HeLa cells. The potentiating effects of these agents for the cytotoxicity of free gelonin varied from marked to nonexistent, depending on the type of cells. In particular, adenovirus- 2 potentiated the cytotoxicity of gelonin for HeLa cells but not for Namalwa cells. The three major adenoviral capsid proteins, penton, hexon, and fiber, were isolated. It was shown that penton potentiated the cytotoxicity of gelonin for HeLa cells and that hexon and fiber had no measurable effect on the cytotoxicity of gelonin. However, like the whole virus, penton was not able to affect the cytotoxicity of gelonin conjugates.

Volume 36, Issue 5, pp. 818-822, 11/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics