rdf:type |
|
lifeskim:mentions |
umls-concept:C0003069,
umls-concept:C0021756,
umls-concept:C0027819,
umls-concept:C0030705,
umls-concept:C0086418,
umls-concept:C0205179,
umls-concept:C0205269,
umls-concept:C0205276,
umls-concept:C0205373,
umls-concept:C1280500,
umls-concept:C1328123,
umls-concept:C1363878
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pubmed:issue |
5
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pubmed:dateCreated |
2003-2-13
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pubmed:abstractText |
In murine models, transgenic chemokine-cytokine tumor vaccines overcome many of the limitations of single-agent immunotherapy by producing the sequence of T-cell attraction followed by proliferation. The safety and immunologic effects of this approach in humans were tested in 21 patients with relapsed or refractory neuroblastoma. They received up to 8 subcutaneous injections of a vaccine combining lymphotactin (Lptn)- and interleukin-2 (IL-2)-secreting allogeneic neuroblastoma cells in a dose-escalating scheme. Severe adverse reactions were limited to reversible panniculitis in 5 patients and bone pain in 1 patient. Injection-site biopsies revealed increased cellularity caused by infiltration of CD4+ and CD8+ lymphocytes, eosinophils, and Langerhans cells. Systemically, the vaccine produced a 2-fold (P =.035) expansion of CD4+ T cells, a 3.5-fold (P =.039) expansion of natural killer (NK) cells, a 2.1-fold (P =.014) expansion of eosinophils, and a 1.6-fold (P =.049) increase in serum IL-5. When restimulated in vitro by the immunizing cell line, T cells collected after vaccination showed a 2.3-fold increase (P =.02) of T-helper (TH2)-type CD3+IL-4+ cells. Supernatant collected from restimulated cells showed increased amounts of IL-4 (11.4-fold; P =.021) and IL-5 (8.7-fold; P =.002). Six patients had significant increases in NK cytolytic activity. Fifteen patients made immunoglobulin G (IgG) antibodies that bound to the immunizing cell line. Measurable tumor responses included complete remission in 2 patients and partial response in 1 patient. Hence, allogeneic tumor cell vaccines combining transgenic Lptn with IL-2 appear to have little toxicity in humans and can induce an antitumor immune response.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, C,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/XCL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/lymphotactin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
|
pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:AlcoserPatP,
pubmed-author:BowmanLaura CLC,
pubmed-author:BrennerMalcolm KMK,
pubmed-author:CooperKristineK,
pubmed-author:DavidoffAndrewA,
pubmed-author:GeeAdrianA,
pubmed-author:GrilleyBambiB,
pubmed-author:HaightAnn EAE,
pubmed-author:Hirschmann-JaxCharlotteC,
pubmed-author:InmanShannonS,
pubmed-author:MeiZhuyongZ,
pubmed-author:PopekEdwinaE,
pubmed-author:RillDonna RDR,
pubmed-author:RousseauRaphaël FRF,
pubmed-author:SmithSusan CSC,
pubmed-author:StrotherDouglasD,
pubmed-author:YvonEric SES
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pubmed:issnType |
Print
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pubmed:day |
1
|
pubmed:volume |
101
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1718-26
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12406881-Adolescent,
pubmed-meshheading:12406881-CD4 Lymphocyte Count,
pubmed-meshheading:12406881-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12406881-Cancer Vaccines,
pubmed-meshheading:12406881-Chemokines, C,
pubmed-meshheading:12406881-Child,
pubmed-meshheading:12406881-Child, Preschool,
pubmed-meshheading:12406881-Cytokines,
pubmed-meshheading:12406881-DNA, Complementary,
pubmed-meshheading:12406881-Female,
pubmed-meshheading:12406881-Humans,
pubmed-meshheading:12406881-Hypersensitivity, Delayed,
pubmed-meshheading:12406881-Immunization Schedule,
pubmed-meshheading:12406881-Immunoglobulin G,
pubmed-meshheading:12406881-Immunophenotyping,
pubmed-meshheading:12406881-Infant,
pubmed-meshheading:12406881-Injections, Subcutaneous,
pubmed-meshheading:12406881-Interleukin-2,
pubmed-meshheading:12406881-Killer Cells, Natural,
pubmed-meshheading:12406881-Lymphokines,
pubmed-meshheading:12406881-Male,
pubmed-meshheading:12406881-Neuroblastoma,
pubmed-meshheading:12406881-Panniculitis,
pubmed-meshheading:12406881-Recombinant Fusion Proteins,
pubmed-meshheading:12406881-Remission Induction,
pubmed-meshheading:12406881-Salvage Therapy,
pubmed-meshheading:12406881-Sialoglycoproteins,
pubmed-meshheading:12406881-Skin,
pubmed-meshheading:12406881-Th2 Cells,
pubmed-meshheading:12406881-Transduction, Genetic,
pubmed-meshheading:12406881-Treatment Outcome,
pubmed-meshheading:12406881-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma.
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pubmed:affiliation |
Center for Cell and Gene Therapy, Texas Children's Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA. rfrousse@txccc.org
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Clinical Trial, Phase I
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