| pubmed-article:9610908 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C0027651 | lld:lifeskim |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C0007134 | lld:lifeskim |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C0079722 | lld:lifeskim |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C0018270 | lld:lifeskim |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C1819447 | lld:lifeskim |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C1511636 | lld:lifeskim |
| pubmed-article:9610908 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:9610908 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:9610908 | pubmed:dateCreated | 1998-7-17 | lld:pubmed |
| pubmed-article:9610908 | pubmed:abstractText | Combination therapy with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes (TILs) demonstrates significant clinical activity in patients with metastatic renal cell carcinoma (RCC). To investigate whether local delivery of IL-2 via gene transfer is capable of improving the potency and efficacy of in vitro propagated TILs as compared with standard growth conditions [400 BRMP U (BU)/ml], a replication-deficient adenovirus expressing the human IL-2 gene under control of the cytomegalovirus (CMV) promoter (Ad-IL-2) has been constructed in our laboratory. RCC-TIL cultures were initiated by directly infecting RCC tumor suspension with Ad-IL-2 at a multiplicity of infection of 10:1. Subsequently the TIL cultures were restimulated with nonirradiated autologous RCC infected with Ad-IL-2 (RCC-Ad-IL-2) every 10 days (TIL/tumor = 50:1). Cell growth, phenotype, cytotoxicity, and cytokine messenger RNA (mRNA) expression were analyzed and compared with TIL growth stimulated with exogenous IL-2 (400 BU/ml). All five TILs tested responded to RCC-Ad-IL-2 activation, and a completed clearance of tumor cells was observed in cultures within 7-10 days. Lysis of nonirradiated RCC-Ad-IL-2 cells by TILs also was observed in cultures 3-5 days after restimulation. The IL-2 concentration in cell culture supernatants was maintained between 10 BU and 35 BU/ml (2 and 7 ng/ml), respectively. When compared with exogenous IL-2, RCC-Ad-IL-2 induced less growth expansion of TILs whereas a reduced CD56+ (23 +/- 14% vs. 44 +/- 13%; p < 0.05) but increased CD3+CD4+ cell population (32 +/- 11% vs. 15 +/- 6%; p < 0.05) with enhanced T cell-receptor use (59 +/- 10% vs. 42 +/- 7%; p < 0.005) was determined. An augmented human leukocyte antigen (HLA)-restricted and tumor-specific cytotoxicity was detected in RCC-Ad-IL-2-expanded TILs (day 35, 15.3 +/- 4.2 LU vs. 4.6 +/- 1.8 LU; p < 0.005). These properties were mediated by the CD8+ and CD4+ T-cell populations, as demonstrated by antibody-blocking assays. A unique cytokine profile also was detected in RCC-Ad-IL-2-induced TILs, which demonstrated an upregulation of both GM-CSF and IL-6 mRNA as compared with TILs expanded in the presence of exogenous IL-2. These data suggest that RCC-Ad-IL-2 is a potent immune stimulant that can be used in vitro as an immunogen to propagate cytotoxic RCC-TILs for adoptive immunotherapy or potentially in vivo by direct injection as a live tumor vaccine. | lld:pubmed |
| pubmed-article:9610908 | pubmed:language | eng | lld:pubmed |
| pubmed-article:9610908 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9610908 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:9610908 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:9610908 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:9610908 | pubmed:month | May | lld:pubmed |
| pubmed-article:9610908 | pubmed:issn | 1524-9557 | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:McBrideW HWH | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:Pai?VV | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:BelldegrunAA | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:TsoC LCL | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:KabooRR | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:FiglinRR | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:DannullJJ | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:GitlitzBB | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:HinkelAA | lld:pubmed |
| pubmed-article:9610908 | pubmed:author | pubmed-author:MuldersPP | lld:pubmed |
| pubmed-article:9610908 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:9610908 | pubmed:volume | 21 | lld:pubmed |
| pubmed-article:9610908 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:9610908 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:9610908 | pubmed:pagination | 170-80 | lld:pubmed |
| pubmed-article:9610908 | pubmed:dateRevised | 2008-3-18 | lld:pubmed |
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| pubmed-article:9610908 | pubmed:meshHeading | pubmed-meshheading:9610908-... | lld:pubmed |
| pubmed-article:9610908 | pubmed:year | 1998 | lld:pubmed |
| pubmed-article:9610908 | pubmed:articleTitle | Adenovirus-mediated interleukin-2 production by tumors induces growth of cytotoxic tumor-infiltrating lymphocytes against human renal cell carcinoma. | lld:pubmed |
| pubmed-article:9610908 | pubmed:affiliation | Department of Urology, The Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California 90024, USA. | lld:pubmed |
| pubmed-article:9610908 | pubmed:publicationType | Journal Article | lld:pubmed |
