Salmonella-Mediated Cytolethal Distending Toxin Transfer Inhibits Tumor Growth.

The Salmonella enterica serovar Choleraesuis (S.C.) has potential as an antitumor agent because of its tumor-targeting characteristics. S.C. can also be used for specific delivery of therapeutic agents and continuous release during replication. Previously, we successfully used S.C. as a vector to transfer a therapeutic gene and oncolytic virus, which suggested that modified S.C. is suitable for incorporating other antitumor agents into a single system. Cytolethal distending toxin B (CdtB) produced by Campylobacter jejuni can induce tumor cell apoptosis. Here we coated CdtB with poly(allylamine hydrochloride) (PAH) to yield PAH-CdtB. Treatment of cells with PAH-coated CdtB induced apoptosis, demonstrating that the compound retained antitumor activity. Furthermore, S.C. coated with PAH-CdtB (CdtB-S.C.) maintained tumor-targeting activity and had an enhanced antitumor effect. Measurement of the cytotoxic effect of CdtB-S.C. in vitro in a tumor cell line showed increased apoptosis whereas treatment of tumor-bearing mice with CdtB-S.C. reduced tumor growth and prolonged survival. Taken together, our results provide evidence that Salmonella carrying CdtB could have application for the treatment of tumors.