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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-1-20
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pubmed:abstractText |
Umbilical cord blood (UCB) T cells can be redirected to kill leukemia and lymphoma cells by engineering with a single-chain chimeric antigen receptor (CAR) and thus may have general applications in adoptive cell therapy. However, the role of costimulatory molecules in UCB T-cell activation and effector functions in context with CAR remains elusive. To investigate the effect of costimulatory molecules (4-1BB and CD28) on UCB T cells, we transduced UCB T cells with lentiviral vectors expressing Green Fluorescent Protein (GFP) and CAR for CD19 containing an intracellular domain of the CD3zeta chain and either a 4-1BB (UCB-19BBzeta) or a CD28 intracellular domain (UCB-1928zeta), both (UCB-1928BBzeta), or neither (UCB-19zeta). We found that UCB-19BBzeta and UCB-28BBzeta T cells exhibited more cytotoxicity to CD19(+) leukemia and lymphoma cell lines than UCB-19zeta and UCB-1928zeta, although differences in secretion of interleukin-2 and interferon-gamma by these T cells were not evident. In vivo adoptive transfer of these T cells into intraperitoneal tumor-bearing mice demonstrated that UCB-19BBzeta and UCB-1928BBzeta T cells mounted the most potent antitumor response. The mice adoptively transferred with UCB-1928BBzeta cells survived longer than the mice with UCB-19BBzeta. Moreover, UCB-1928BBzeta T cells mounted a more robust antitumor response than UCB-19BBzeta in a systemic tumor model. Our data suggest a synergistic role of 4-1BB and CD28 costimulation in engineering antileukemia UCB effector cells and implicate a design for redirected UCB T-cell therapy for refractory leukemia.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-10417377,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-10680014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-11753365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-12393484,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-12509765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-12579196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-12835672,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-12946996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-12946999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-14688315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-14961035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-15032595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-15233937,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-15619618,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-15626734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-15771565,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-15979412,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-16352804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-16734614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-1691237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-16932339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-17108138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-17119120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-17145367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-17656004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-17685852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-17855649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-17878391,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-18024793,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-18227839,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-18354418,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-18645038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-18684977,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-19384291,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-7892281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-8421711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-9155647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-9705944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19719389-9743337
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1557-7422
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
75-86
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:19719389-Humans,
pubmed-meshheading:19719389-Animals,
pubmed-meshheading:19719389-Mice,
pubmed-meshheading:19719389-Leukemia,
pubmed-meshheading:19719389-Lymphoma,
pubmed-meshheading:19719389-Fetal Blood,
pubmed-meshheading:19719389-Transduction, Genetic,
pubmed-meshheading:19719389-Cytotoxicity, Immunologic,
pubmed-meshheading:19719389-Cell Line, Tumor,
pubmed-meshheading:19719389-T-Lymphocytes,
pubmed-meshheading:19719389-B-Lymphocytes,
pubmed-meshheading:19719389-Signal Transduction,
pubmed-meshheading:19719389-Interleukin-2,
pubmed-meshheading:19719389-Recombinant Proteins,
pubmed-meshheading:19719389-Interferon-gamma,
pubmed-meshheading:19719389-Immunophenotyping,
pubmed-meshheading:19719389-Antigens, CD28
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