| Autor: |
Rudginsky S; Genzyme Corporation, Framingham, Massachusetts 01701, USA., Siders W, Ingram L, Marshall J, Scheule R, Kaplan J |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2001 Oct; Vol. 4 (4), pp. 347-55. |
| DOI: |
10.1006/mthe.2001.0463 |
| Abstrakt: |
We previously reported that treatment of intraperitoneal tumors with complexes of cationic lipid and noncoding plasmid DNA leads to the development of a specific, cytotoxic T-cell response correlating with the rejection of established tumor cells as well as subsequent tumor re-challenge. Here, focusing on an intraperitoneal AB12 mesothelioma model, we show that the anticancer effects of the lipid:DNA complex are associated with DNA containing immunostimulatory CpG motifs. Complexes prepared with cationic lipid and bacterial plasmid DNA, Escherichia coli genomic DNA fragments, or synthetic immunostimulatory CpG oligodeoxynucleotides provided a substantial survival benefit, whereas eukaryotic DNA and methylated bacterial DNA had little or no therapeutic activity. Alternative inflammatory stimuli such as thioglycolate, poly(I:C), and incomplete or complete Freund's adjuvant failed to reproduce the antitumor activity obtained with the lipid:DNA complex. The innate immune response triggered by lipid:DNA complexes led to the development of a systemic immune response against tumor cells that allowed animals to reject tumors not only at the intraperitoneal treatment site, but also at a distal subcutaneous site. These data demonstrate that immunostimulatory DNA complexed with cationic lipid is a potent inducer of innate and adaptive immune responses against tumor cells and represents a potentially useful tool in the immunotherapy of cancers for which tumor-associated antigens have not been identified. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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