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Vaccine. 2004 Jun 23;22(19):2480-8.

Development of immunomodulatory six base-length non-CpG motif oligonucleotides for cancer vaccination.

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  • 1Bioniche Therapeutics Division, Bioniche Life Sciences, 6100 Royalmount Avenue, Montréal, Que., Canada, H4P 2R2. mario.filion@bioniche.com

Abstract

We have previously described a novel family of immunomodulatory synthetic oligonucleotides characterized by a phosphodiester backbone, a length of six bases and a 5'G3xG23' sequence, where x is A, C, G or T. In the present study, we have evaluated whether these 5'G3xG23' oligonucleotides possess additional activities essential for adequate cancer vaccination. Immunization for the treatment of cancer requires an adjuvant, a source of tumor-associated antigen(s), for example apoptotic cancer cells, and a way to overcome the escape of tumor cells from the immune system, for example the up-regulation of Fas ligand (FasL) on the surface of cancer cells. The results show that phosphodiester 5'G3AG23' and 5'G3TG23' oligonucleotides have a direct activity on a number of different cancer cells by inducing apoptosis (release of cytochrome C, activation of caspase-3, cleavage of poly [ADP-ribose] polymerase, degradation of nuclear mitotic apparatus protein and translocation of phophatidylserine at the cell surface). In addition, the 5'G3AG23', 5'G3CG23', and 5'G3TG23' oligonucleotides were found to down-regulate the levels of FasL on the surface of cancer cells. These immunomodulatory phosphodiester six base-length oligonucleotides, which are capable of inducing apoptosis in cancer cells as well as downregulating the expression of FasL at their cell surface, may have application as cancer cell vaccines.

PMID:
15193412
[PubMed - indexed for MEDLINE]
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