Abstract:
:The bystander effect is an important part of tumor kill using gene-directed enzyme prodrug therapy (GDEPT). Recently, we have described a novel enzyme prodrug system using bacterial nitroreductase and the prodrug CB1954 (NTR/CB1954). We demonstrate here the presence of a cell-permeable cytotoxic activity in the conditioned growth medium of nitroreductase (NTR)-transduced cells treated with CB1954 and show that its appearance corresponds to the appearance of two metabolites of CB1954 previously identified (Friedlos et al., 1992). The degree of bystander effect and the degree of transferred cytotoxicity correlates with the level of NTR enzyme expression. Two other prodrugs for NTR show little bystander killing and do not produce detectable cell permeable metabolites. The elucidation of the mechanism of the bystander effect may allow the more effective use of NTR/CB1954.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Bridgewater JA,Knox RJ,Pitts JD,Collins MK,Springer CJdoi
10.1089/hum.1997.8.6-709subject
Has Abstractpub_date
1997-04-10 00:00:00pages
709-17issue
6eissn
1043-0342issn
1557-7422journal_volume
8pub_type
杂志文章abstract::To achieve effective gene therapy, it is necessary to selectively and efficiently transfect therapeutic gene into targeted cells. In this study, we developed a combination method using mannosylated lipoplexes, which show selectivity to antigen-presenting cells such as macrophages and dendritic cells, and bubble liposo...
journal_title:Human gene therapy
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journal_title:Human gene therapy
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abstract::Replication-deficient adenoviruses are known to induce acute injury and inflammation of infected tissues, thus limiting their use for human gene therapy. However, molecular mechanisms triggering this response have not been fully defined. To characterize this response, chemokine expression was evaluated in DBA/2 mice f...
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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