| pubmed-article:11691814 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C0008109 | lld:lifeskim |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C0018183 | lld:lifeskim |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C0007134 | lld:lifeskim |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C0162768 | lld:lifeskim |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C1521761 | lld:lifeskim |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C1948023 | lld:lifeskim |
| pubmed-article:11691814 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:11691814 | pubmed:issue | 21 | lld:pubmed |
| pubmed-article:11691814 | pubmed:dateCreated | 2001-11-5 | lld:pubmed |
| pubmed-article:11691814 | pubmed:abstractText | Immunotherapy targeting for the induction of a T-cell-mediated antitumor response in patients with renal cell carcinoma (RCC) appears to hold significant promise. Here we describe a novel RCC vaccine strategy that allows for the concomitant delivery of dual immune activators: G250, a widely expressed RCC associated antigen; and granulocyte/macrophage-colony stimulating factor (GM-CSF), an immunomodulatory factor for antigen-presenting cells. The G250-GM-CSF fusion gene was constructed and expressed in Sf9 cells using a baculovirus expression vector system. The Mr 66,000 fusion protein (FP) was subsequently purified through a 6xHis-Ni2+-NTA affinity column and SP Sepharose/fast protein liquid chromatography. The purified FP retains GM-CSF bioactivity, which is comparable, on a molar basis, to that of recombinant GM-CSF when tested in a GM-CSF-dependent cell line. When combined with interleukin 4 (IL-4; 1000 units/ml), FP (0.34 microg/ml) induces differentiation of monocytes (CD14+) into dendritic cells (DCs) expressing surface markers characteristic for antigen-presenting cells. Up-regulation of mature DCs (CD83+CD19-; 17% versus 6%) with enhanced expression of HLA class I and class II antigens was detected in FP-cultured DCs as compared with DCs cultured with recombinant GM-CSF. Treatment of peripheral blood mononuclear cells (PBMCs) with FP alone (2.7 microg/10(7) cells) augments both T-cell helper 1 (Th1) and Th2 cytokine mRNA expression (IL-2, IL-4, GM-CSF, IFN-gamma, and tumor necrosis factor-alpha). Comparison of various immune manipulation strategies in parallel, bulk PBMCs treated with FP (0.34 microg/ml) plus IL-4 (1000 units/ml) for 1 week and restimulated weekly with FP plus IL-2 (20 IU/ml) induced maximal growth expansion of active T cells expressing the T-cell receptor and specific anti-RCC cytotoxicity, which could be blocked by the addition of anti-HLA class I, anti-CD3, or anti-CD8 antibodies. In one tested patient, an augmented cytotoxicity against lymph node-derived RCC target was determined as compared with that against primary tumor targets, which corresponded to an 8-fold higher G250 mRNA expression in lymph node tumor as compared with primary tumor. The replacement of FP with recombinant GM-CSF as an immunostimulant completely abrogated the selection of RCC-specific killer cells in peripheral blood mononuclear cell cultures. All FP-modulated peripheral blood mononuclear cell cultures with antitumor activity showed an up-regulated CD3+CD4+ cell population. These results suggest that GM-CSF-G250 FP is a potent immunostimulant with the capacity for activating immunomodulatory DCs and inducing a T-helper cell-supported, G250-targeted, and CD8+-mediated antitumor response. These findings may have important implications for the use of GM-CSF-G250 FP as a tumor vaccine for the treatment of patients with advanced kidney cancer. | lld:pubmed |
| pubmed-article:11691814 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11691814 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11691814 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11691814 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11691814 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11691814 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11691814 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11691814 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11691814 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11691814 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11691814 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:11691814 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:HernandezJ... | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:PaimUU | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:NguyenDD | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:de KernionJJ | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:ZismanAA | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:PantuckAA | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:BelldegrunAA | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:TsoC LCL | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:FiglinRR | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:GitlitzBB | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:CalilliwRR | lld:pubmed |
| pubmed-article:11691814 | pubmed:author | pubmed-author:ShintakuP IPI | lld:pubmed |
| pubmed-article:11691814 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11691814 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:11691814 | pubmed:volume | 61 | lld:pubmed |
| pubmed-article:11691814 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11691814 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11691814 | pubmed:pagination | 7925-33 | lld:pubmed |
| pubmed-article:11691814 | pubmed:dateRevised | 2005-11-17 | lld:pubmed |
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| pubmed-article:11691814 | pubmed:meshHeading | pubmed-meshheading:11691814... | lld:pubmed |
| pubmed-article:11691814 | pubmed:year | 2001 | lld:pubmed |
| pubmed-article:11691814 | pubmed:articleTitle | Induction of G250-targeted and T-cell-mediated antitumor activity against renal cell carcinoma using a chimeric fusion protein consisting of G250 and granulocyte/monocyte-colony stimulating factor. | lld:pubmed |
| pubmed-article:11691814 | pubmed:affiliation | Department of Urology, UCLA Kidney Cancer Program, University of California Los Angeles, Los Angeles, California 90095, USA. | lld:pubmed |
| pubmed-article:11691814 | pubmed:publicationType | Journal Article | lld:pubmed |
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