1999
DOI: 10.1038/sj.bmt.1701801
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Clinical use of streptolysin-O to facilitate antisense oligodeoxyribonucleotide delivery for purging autografts in chronic myeloid leukaemia

Abstract: Summary:Antisense oligodeoxyribonucleotides (ODN) targeted against the breakpoint in BCR-ABL mRNA will specifically decrease BCR-ABL mRNA, provided cells are first permeabilised with streptolysin-O (SL-O). We used 18-mer chimeric methylphosphonodiester: phosphodiester linked (4-9-4) ODN complementary to 9 bases either side of the BCR-ABL junction to purge harvests ex vivo in three CML patients who remained completely Ph positive after multiple chemotherapy courses. After CD34 ؉ cell selection and SL-O permeabi… Show more

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Cited by 22 publications
(16 citation statements)
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“…Alternative delivery strategies, including the use of various lipid transfecting agents, liposomes, cationic polyelectrolytes, and physical methods for membrane permeabilization, could reasonably be expected to improve delivery still further. [67][68][69] At the same time, results reported here suggest that enhanced delivery may also increase cell toxicity, at least with the anti-Myb ODN, and potentially with other ODNs that target genes required by both normal and malignant cells. In this regard, it is worth noting that the 72-hour purge appeared more efficient than the 24-hour exposure, but unacceptable lowering of the compound's therapeutic index was suggested by the prolonged marrow aplasia observed in 3 patients.…”
Section: Discussionmentioning
confidence: 67%
See 1 more Smart Citation
“…Alternative delivery strategies, including the use of various lipid transfecting agents, liposomes, cationic polyelectrolytes, and physical methods for membrane permeabilization, could reasonably be expected to improve delivery still further. [67][68][69] At the same time, results reported here suggest that enhanced delivery may also increase cell toxicity, at least with the anti-Myb ODN, and potentially with other ODNs that target genes required by both normal and malignant cells. In this regard, it is worth noting that the 72-hour purge appeared more efficient than the 24-hour exposure, but unacceptable lowering of the compound's therapeutic index was suggested by the prolonged marrow aplasia observed in 3 patients.…”
Section: Discussionmentioning
confidence: 67%
“…57,76 In our view, 2 smaller ODN purging studies (3 and 8 patients, respectively) carried out on CML patients appear to support these points. 68,77 These trials differed from our own in a number of respects, but the most fundamental differences were that both used oligonucleotides directed against the bcr/abl oncogene. If the data provided in those reports are compared with those reported here, the anti-Myb ODN appeared to have greater activity against its target gene.…”
Section: Discussionmentioning
confidence: 99%
“…Future investigations will extend this research to experimental animal models to validate the role of AAH in neuroblastoma cell invasion in vivo. Successful application of antisense ODNs to specifically inhibit gene expression in mammalian cells has been reported by a number of investigators using both in vitro and in vivo models (Broughton et al, 1997;Clark et al, 1999;Dinchuk et al, 2000;Faria et al, 2001;Wagner, 1994;Wakita and Wands, 1994;Zimrin et al, 1996). Previous limitations surrounding the in vivo use of antisense gene therapy were a result of low physiologic stability, slow cellular uptake, and inadequate tissue specificity of the ODNs.…”
Section: Sepe Et Almentioning
confidence: 99%
“…Two cases achieved lasting haematological benefit, although with cytogenetic evidence of persisting disease. 114 A common theme of each of these reports is that engraftment may be delayed following antisense purged transplantation, although this does not appear to have resulted in significant adverse clinical problems over and above those expected following an unpurged autograft. Some patients, notably those with advanced disease, appear to have derived clinical benefit, though not cure, although it is very difficult to divorce the effect of purging from that achievable with an unpurged graft.…”
Section: Odn As Ex Vivo Purging Agentsmentioning
confidence: 99%