Establishment of a new gene therapy for cancer using antisense ODG and atelocollagen

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Background and Aims: Substantial evidence supports a direct role of ornitine decarboxylase (ODC) in the development and maintenance of human tumors. Although antisenseoligonucleotide therapy targeting various genes are useful for cancer treatment, one of the major limitations is the problem of delivery. We describe here a novel antisense oligonucleotide delivery method which allows prolonged sustainment and release of ODC antisense oligonucleotides in vivo using atelocollagen. Methods: The effect of ODC antisense oligonucleotides in the atelocollagen on cell growth of gastrointestinal cancer (MKN 45 and COLO201), and rhabdomyosarcoma (RD) was studied in vitro using MTT assay. In vivo, the effect of intratumoral, intramuscular and intraperitoneal single administration of ODC antisense oligonucleotides in the atelocollagen on tumor growth of MKN45, COLO201 and RD cells was examined. ODC activity and polyamine contents were measured. Results: In vitro, ODC antisense oligonucleotides in the atelocollagen remarkably suppressed MKN45, COLO201 and RD cell growth. A single administration of antisense oligonucleotides in the atelocollagen via three routes remarkably suppressed the growth of MKN45, COLO201 and RD tumor over a period of 3542 days. Conclusion: As various human cancers significantly express ODC, the results strongly suggest that this new antisense method may be of considerable value for treatment of human cancers.