Source:http://linkedlifedata.com/resource/pubmed/id/11830482
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2002-2-6
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| pubmed:abstractText |
A recombinant anti-CD25 immunotoxin, LMB-2, has shown clinical efficacy in hairy cell leukemia and T-cell neoplasms. Its activity in B-cell chronic lymphocytic leukemia (B-CLL) is inferior but might be improved if B-CLL cells expressed higher numbers of CD25 binding sites. It was recently reported that DSP30, a phosphorothioate CpG-oligodeoxynucleotide (CpG-ODN) induces immunogenicity of B-CLL cells by up-regulation of CD25 and other antigens. The present study investigated the antitumor activity of LMB-2 in the presence of DSP30. To this end, B-CLL cells from peripheral blood of patients were isolated immunomagnetically to more than 98% purity. Incubation with DSP30 for 48 hours augmented CD25 expression in 14 of 15 B-CLL samples, as assessed by flow cytometry. DSP30 increased LMB-2 cytotoxicity dose dependently whereas a control ODN with no CpG motif did not. LMB-2 displayed no antitumor cell activity in the absence of CpG-ODN as determined colorimetrically with an (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. In contrast, B-CLL growth was inhibited in 12 of 13 samples with 50% inhibition concentrations (IC(50)) in the range of LMB-2 plasma levels achieved in clinical studies. Two samples were not evaluable because of spontaneous B-CLL cell death in the presence of DSP30. Control experiments with an immunotoxin that does not recognize hematopoietic cells, and an anti-CD22 immunotoxin, confirmed that sensitization to LMB-2 was specifically due to up-regulation of CD25. LMB-2 was much less toxic to normal B and T lymphocytes compared with B-CLL cells. In summary, immunostimulatory CpG-ODNs efficiently sensitize B-CLL cells to a recombinant immunotoxin by modulation of its target. This new treatment strategy deserves further attention.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/B3(Fv)-PE38KDEL recombinant...,
http://linkedlifedata.com/resource/pubmed/chemical/CPG-oligonucleotide,
http://linkedlifedata.com/resource/pubmed/chemical/Exotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
99
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1320-6
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11830482-Adjuvants, Immunologic,
pubmed-meshheading:11830482-Adult,
pubmed-meshheading:11830482-Aged,
pubmed-meshheading:11830482-Aged, 80 and over,
pubmed-meshheading:11830482-Antibodies, Monoclonal,
pubmed-meshheading:11830482-Antineoplastic Agents,
pubmed-meshheading:11830482-Drug Synergism,
pubmed-meshheading:11830482-Drug Therapy, Combination,
pubmed-meshheading:11830482-Exotoxins,
pubmed-meshheading:11830482-Female,
pubmed-meshheading:11830482-Humans,
pubmed-meshheading:11830482-Immunotoxins,
pubmed-meshheading:11830482-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:11830482-Male,
pubmed-meshheading:11830482-Middle Aged,
pubmed-meshheading:11830482-Oligodeoxyribonucleotides,
pubmed-meshheading:11830482-Receptors, Interleukin-2,
pubmed-meshheading:11830482-Recombinant Proteins,
pubmed-meshheading:11830482-Thionucleotides,
pubmed-meshheading:11830482-Tumor Cells, Cultured,
pubmed-meshheading:11830482-Up-Regulation
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| pubmed:year |
2002
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| pubmed:articleTitle |
Sensitization of B-cell chronic lymphocytic leukemia cells to recombinant immunotoxin by immunostimulatory phosphorothioate oligodeoxynucleotides.
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| pubmed:affiliation |
3rd Department of Medicine, Technical University of Munich, Munich, Germany. t.decker@lrz.tum.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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