Source:http://linkedlifedata.com/resource/pubmed/id/10878363
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2000-8-3
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| pubmed:abstractText |
The use of anti-CD3 x antitumor bispecific Abs is an attractive and highly specific approach in cancer therapy. Recombinant Ab technology now provides powerful tools to enhance the potency of such immunotherapeutic constructs. We designed a heterodimeric diabody specific for human CD19 on B cells and CD3epsilon chain of the TCR complex. After production in Escherichia coli and purification, we analyzed its affinity, stability, and pharmacokinetics, and tested its capacity to stimulate T cell proliferation and mediate in vitro lysis of CD19+ tumor cells. The effect of the diabody on tumor growth was investigated in an in vivo model using immunodeficient mice bearing a human B cell lymphoma. The CD3 x CD19 diabody specifically interacted with both CD3- and CD19-positive cells, was able to stimulate T cell proliferation in the presence of tumor cells, and induced the lysis of CD19+ cells in the presence of activated human PBL. The lytic potential of the diabody was enhanced in the presence of an anti-CD28 mAb. In vivo experiments indicated a higher stability and longer blood retention of diabodies compared with single chain Fv fragments. Treatment of immunodeficient mice bearing B lymphoma xenografts with the diabody and preactivated human PBL efficiently inhibited tumor growth. The survival time was further prolonged by including the anti-CD28 mAb. The CD3 x CD19 diabody is a powerful tool that should facilitate the immunotherapy of minimal residual disease in patients with B cell leukemias and malignant lymphomas.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Bispecific,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD19,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor-CD3 Complex, Antigen...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
165
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
888-95
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10878363-Animals,
pubmed-meshheading:10878363-Antibodies, Bispecific,
pubmed-meshheading:10878363-Antigens, CD19,
pubmed-meshheading:10878363-Antineoplastic Agents,
pubmed-meshheading:10878363-Binding Sites, Antibody,
pubmed-meshheading:10878363-Gene Expression,
pubmed-meshheading:10878363-Humans,
pubmed-meshheading:10878363-Jurkat Cells,
pubmed-meshheading:10878363-Lymphoma, B-Cell,
pubmed-meshheading:10878363-Male,
pubmed-meshheading:10878363-Mice,
pubmed-meshheading:10878363-Mice, Knockout,
pubmed-meshheading:10878363-Neoplasm Transplantation,
pubmed-meshheading:10878363-Receptor-CD3 Complex, Antigen, T-Cell,
pubmed-meshheading:10878363-Recombinant Proteins,
pubmed-meshheading:10878363-T-Lymphocytes,
pubmed-meshheading:10878363-Transplantation, Heterologous,
pubmed-meshheading:10878363-Tumor Cells, Cultured
|
| pubmed:year |
2000
|
| pubmed:articleTitle |
Treatment of human B cell lymphoma xenografts with a CD3 x CD19 diabody and T cells.
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| pubmed:affiliation |
Recombinant Antibody Research Group, Department of Tumor Progression and Immune Defense, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|