Linked Life Data

10880024

Source:http://linkedlifedata.com/resource/pubmed/id/10880024

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-10-18
pubmed:abstractText
Generation of an efficient graft-versus-leukemia (GVL) effect in patients with hematological malignancies who relapse after allogeneic bone marrow transplantation depends in part upon the number of infused T lymphocytes. Currently, a GVL reaction cannot be achieved without inducing concomitant graft-versus-host disease (GVHD); thus, one strategy is to try to modulate this GVL/GVHD ratio. We engineered human T lymphocytes with herpes simplex virus-thymidine kinase and neomycin resistance genes, with an LXSN-derived vector that confers a ganciclovir-specific sensitivity to the transduced T cells. We analyzed proliferation, interleukin-2 production, alloreactivity in a mixed lymphocyte culture, and clonogenicity during the different stages of retroviral infection and G418 selection. Our results confirm that a sufficient number of transduced T lymphocytes can be obtained after selection for clinical studies. Their proliferative activity, alloresponsiveness, and ability to produce and respond to interleukin-2 were retained. Compared with control populations, their clonogenicity, as assessed by limiting dilution assays, was reduced after retroviral infection and G418 selection by 1.6 and 2.9 logs, respectively, with both viral supernatant incubation and coculture procedures. This study shows that infection and selection with the thymidine kinase-neomycin resistance gene retroviral vector significantly reduces the number of functional T lymphocytes. This finding should be taken into account when establishing the dose of T lymphocytes necessary to trigger a modulated GVL/GVHD effect.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0929-1903
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
920-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10880024-Anti-Bacterial Agents, pubmed-meshheading:10880024-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:10880024-Cells, Cultured, pubmed-meshheading:10880024-DNA Primers, pubmed-meshheading:10880024-Dose-Response Relationship, Drug, pubmed-meshheading:10880024-Flow Cytometry, pubmed-meshheading:10880024-Ganciclovir, pubmed-meshheading:10880024-Gene Transfer Techniques, pubmed-meshheading:10880024-Gentamicins, pubmed-meshheading:10880024-Humans, pubmed-meshheading:10880024-Interleukin-2, pubmed-meshheading:10880024-Lymphocyte Activation, pubmed-meshheading:10880024-Polymerase Chain Reaction, pubmed-meshheading:10880024-Retroviridae, pubmed-meshheading:10880024-Simplexvirus, pubmed-meshheading:10880024-T-Lymphocytes, pubmed-meshheading:10880024-Thymidine Kinase, pubmed-meshheading:10880024-Time Factors
pubmed:year
2000
pubmed:articleTitle
T-lymphocyte function after retroviral-mediated thymidine kinase gene transfer and G418 selection.
pubmed:affiliation
Sections of Haematology and Clinical Immunology, Department of Clinical and Experimental Medicine, Perugia University, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't