Enhancement of toxicity of antitransferrin receptor antibody-Pseudomonas exotoxin conjugates by adenovirus.

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Abstract
Cytotoxic conjugates were constructed by chemically coupling Pseudomonas exotoxin to antitransferrin receptor antibodies. Toxicity of these conjugates for human oral carcinoma KB cells, due to entry via the transferrin receptor, was enhanced 100- to 300-fold in the presence of adenovirus. By EM and immunofluorescence it was determined that antitransferrin receptor antibodies and the conjugates derived from them entered cells from coated pits into receptosomes. The enhanced toxicity evidently resulted when adenovirus and the toxin conjugates were internalized into the same receptosomes. In the process of infection, adenovirus enters cells and brings about a virus-mediated disruption of receptosomes; this disruption can liberate many more toxin molecules into the cytosol than is possible in the absence of virus. These results are relevant to the production of more effective immunotoxin conjugates for cancer treatment.