Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-11-17
pubmed:abstractText
Anti-thymocyte globulins (ATG) are currently used to prevent graft-versus-host disease in haematopoietic stem cell transplants from alternative donors and to treat and prevent acute organ rejection after transplantation. Many recent studies have demonstrated that ATG can also be beneficial in patients with myeloma, lymphoma, leukaemia and myelodysplastic syndrome. This study showed, for the first time, that the cytotoxic effect of ATG can been enhanced by conjugation with saporin-S6, which is one of the most stable and active type-1 ribosome-inactivating proteins. The ATG-saporin-S6 immunotoxin showed a strong cytotoxic effect on five lymphoma- and leukaemia-derived cell lines as well as on activated lymphocytes while sparing non-haematological cell lines. ATG-saporin-S6 induced a time-dependent activation of caspase-3/7 in RAJI cells. The caspase inhibitor Z-VAD-fmk partially rescued the cells that were treated with ATG-saporin-S6, suggesting that multiple cell death pathways, some of which are caspase independent, play a role in ATG-saporin-S6 toxicity. In our experiments ATG increased the complement-independent cytotoxicity of activated lymphocytes by a magnitude of 3-5 logs after conjugation. These findings suggest that the ATG-saporin-S6 immunotoxin is a promising therapeutic tool for many pathological conditions involving T lymphocytes and T and B neoplastic cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1365-2141
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
147
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
710-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
ATG-saporin-S6 immunotoxin: a new potent and selective drug to eliminate activated lymphocytes and lymphoma cells.
pubmed:affiliation
Dipartimento di Patologia Sperimentale, Università di Bologna, Bologna, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't