Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1993-2-5
pubmed:abstractText
Recent experiments with genetically engineered tumors have generated renewed interest in active cellular immunotherapy as a cancer treatment modality. In order to consider the use of live tumor cells for immunotherapy in human cancer patients, it will be important to ensure that these cells do not themselves produce morbidity in the event the immune system fails to eliminate them. Toward this end, we have examined a strategy for eliminating genetically manipulated nonimmunogenic tumors in vivo. When B16F10 melanoma cells were transfected with the Herpes simplex virus 1 thymidine kinase (HSV-TK) gene, cells were rendered susceptible to killing by the nucleoside analogs acyclovir (ACV) and ganciclovir (GCV). B16-HSV-TK+ tumors established in C57BL6 mice were successfully "suicided" in vivo when GCV was administered by continuous infusion. However, late recurrences were observed even after 1 month of continuous GCV treatment. In vivo growth kinetics suggested that the recurrences resulted from a tiny number (< 20) of cells that had survived the GCV treatment. Interestingly, recurrent tumors were as sensitive to GCV as the parental B16-HSV-TK+ line. While these results demonstrate potential feasibility of the suicide gene strategy for active immunotherapy with live tumor cells, they also illustrate that approaches dependent on the intracellular generation of cell cycle-dependent toxins may fail to eliminate small numbers of cells that temporarily exit cell cycle or that are pharmacologically sequestered.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1053-8550
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
224-30
pubmed:dateRevised
2008-3-18
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Herpes simplex-1 virus thymidine kinase gene is unable to completely eliminate live, nonimmunogenic tumor cell vaccines.
pubmed:affiliation
Department of Medicine, Johns Hopkins University, Baltimore, MD 21205.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't