Linked Life Data

10411920

Source:http://linkedlifedata.com/resource/pubmed/id/10411920

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1999-8-23
pubmed:abstractText
Induction, maintenance, and amplification of tumor-protective immunity after cytokine gene therapy is essential for the clinical success of immunotherapeutic approaches. We investigated whether this could be achieved by single-chain IL-12 (scIL-12) gene therapy followed by tumor-targeted IL-2 using a fusion protein containing a tumor-specific recombinant anti-ganglioside GD(2) antibody and IL-2 (ch14.18-IL-2) in a poorly immunogenic murine neuroblastoma model. Herein, we demonstrate the absence of liver and bone marrow metastases after a lethal challenge with NXS2 wild-type cells only in mice (five of six animals) vaccinated with scIL-12-producing NXS2 cells and given a booster injection of low-dose ch14.18-IL-2 fusion protein. This tumor-protective immunity was effective 3 months after initial vaccination, in contrast to control animals treated with a nonspecific fusion protein or an equivalent mixture of antibody and IL-2. Only vaccinated mice receiving the tumor-specific ch14.18-IL-2 fusion protein revealed a reactivation of CD8(+) T cells and subsequent MHC class I-restricted tumor target cell lysis in vitro. The sequential increase in the usage of TCR chains Vbeta11 and -13 in mouse CD8(+) T cells after vaccination and amplification with ch14.18-IL-2 suggests that the initial polyclonal CD8(+) T cell response is effectively boosted by targeted IL-2. In conclusion, we demonstrate that a successful boost of a partially protective memory T cell immune response that is induced by scIL-12 gene therapy could be generated by tumor-specific targeting of IL-2 with a ch14.18-IL-2 fusion protein. This approach could increase success rates of clinical cancer vaccine trials.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-1741398, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-1745, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-1850114, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-2184369, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-7576970, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-7937818, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8104409, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8610104, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8620623, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8642346, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8647959, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8671670, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8755561, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8978404, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-8981927, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9211416, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9354462, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9362156, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9473237, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9482910, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9500606, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9585204, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9731068, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9731503, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9739060, http://linkedlifedata.com/resource/pubmed/commentcorrection/10411920-9816154
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8591-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:10411920-Animals, pubmed-meshheading:10411920-Antibodies, Neoplasm, pubmed-meshheading:10411920-Antineoplastic Agents, pubmed-meshheading:10411920-CD8-Positive T-Lymphocytes, pubmed-meshheading:10411920-Cancer Vaccines, pubmed-meshheading:10411920-Disease Models, Animal, pubmed-meshheading:10411920-Gangliosides, pubmed-meshheading:10411920-Gene Therapy, pubmed-meshheading:10411920-Immunotherapy, pubmed-meshheading:10411920-Interleukin-12, pubmed-meshheading:10411920-Interleukin-2, pubmed-meshheading:10411920-Mice, pubmed-meshheading:10411920-Neoplasm Transplantation, pubmed-meshheading:10411920-Neuroblastoma, pubmed-meshheading:10411920-Receptors, Antigen, T-Cell, pubmed-meshheading:10411920-Recombinant Fusion Proteins, pubmed-meshheading:10411920-Tumor Cells, Cultured, pubmed-meshheading:10411920-Vaccination
pubmed:year
1999
pubmed:articleTitle
Tumor-targeted IL-2 amplifies T cell-mediated immune response induced by gene therapy with single-chain IL-12.
pubmed:affiliation
The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't