Antitumour Efficacy of the Novel Chemotherapeutic Agent Coramsine is Potentiated by Cotreatment With CpG-Containing Oligodeoxynucleotides

Robbert Van Der Most, Robyn Himbeck, S. Aarons, S.J. Carter, Irma Larma, Cleo Robinson, Andrew Currie, Richard Lake

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Coramsine is a novel chemotherapeutic agent isolated from Solanum linnaeanum (devil's apple). Topical treatment provides clinical benefit for skin tumors. To evaluate the potential broader applicability of the drug, its in vivo anticancer efficacy in a murine model of malignant mesothelioma and its mode of action were investigated. Systemic administration of coramsine slowed tumor growth and prolonged survival time. Importantly, the antitumor efficacy of coramsine was enhanced when treatment was combined with stimulation of innate immunity using unmethylated CpG-containing oligodeoxynucleotides (ODNs). Combination treatment further slowed tumor growth and provided a survival benefit. Coramsine seems to kill tumor cells by direct cell lysis. Using 2 different assays to detect apoptosis (caspase activation and DNA fragmentation), we found no evidence that coramsine induces any form of programmed cell death. The fact that the efficacy of coramsine is potentiated by CpG ODNs suggests that coramsine-induced cell death is an immunologic null event.
Original languageEnglish
Pages (from-to)134-142
JournalJournal of Immunotherapy
Volume29
Issue number2
DOIs
Publication statusPublished - 2006

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