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Clinical Cancer Research Vol. 9, 6516-6522, December 15, 2003
© 2003 American Association for Cancer Research


Experimental Therapeutics, Preclinical Pharmacology

Antitumor Therapy with Bacterial DNA and Toxin

Complete Regression of Established Tumor Induced by Liposomal CpG Oligodeoxynucleotides plus Interleukin-13 Cytotoxin

Ken J. Ishii1, Koji Kawakami2, Ihsan Gursel1, Jacqueline Conover1, Bharat H. Joshi2, Dennis M. Klinman1 and Raj K. Puri2

1 Division of Viral Products and
2 Division of Cellular and Gene Therapies, Center for Biologics Evaluation Research, United States Food and Drug Administration, Bethesda, Maryland

Despite urgent need, no single strategy has been widely effective at controlling the growth of rapidly progressive solid tumors. We demonstrate here a potent antitumor therapy using modified bacterial DNA and toxin. Treatment of human head and neck cancer established as xenografts in athymic mice with immunostimulatory CpG oligodeoxynucleotides encapsulated in sterically stabilized cationic liposome [(CpG ODN)SSCL] and recombinant interleukin-13 Pseudomonas exotoxin (IL13-PE) significantly reduced the tumor growth followed by complete regression in most animals. The antitumor activity of (CpG ODN)SSCL was dependent on natural killer cells that infiltrated within tumors. Interestingly, IL13-PE enhanced (CpG ODN)SSCL-induced natural killer cell activity and cytokine production in vivo and in vitro. These data strongly suggest that a combination of innate immune activation by (CpG ODN)SSCL and tumor-directed targeting by IL13-PE is a novel approach for human cancer immunotherapy.




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Copyright © 2003 by the American Association for Cancer Research.