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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


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.

[PubMed - indexed for MEDLINE]
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