Salmonella-Mediated Cytolethal Distending Toxin Transfer Inhibits Tumor Growth

Wei Kuang Wang, Wei Cheng Chiang, Chih Ho Lai, Che Hsin Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1327-1335
Number of pages9
JournalHuman Gene Therapy
Volume29
Issue number11
DOIs
StatePublished - 11 2018

Bibliographical note

Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc., publishers 2018.

Keywords

  • Salmonella, cytolethal distending toxin, polymer, tumor targeting

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