Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic renal-cell carcinoma (RCC) is not responsive to conventional cytotoxic chemotherapy, but a subset of patients achieve a durable remission with the use of interleukin-2 (IL-2). IL-2 is currently the only Food and Drug Administration (FDA)-approved treatment for metastatic RCC, and it benefits 10-20% of those who receive it. However, it is accompanied by significant, occasionally life-threatening toxicity. Attempts to maintain the efficacy of IL-2 while minimizing systemic side effects have led to the development of IL-2 gene therapies. Leuvectin is a plasmid DNA/lipid complex composed of a plasmid DNA expression vector (VCL-1102, 30) encoding human IL-2 complexed in a 5:1 mass ratio with DMRIE/DOPE lipid (1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidyl ethanolamine), which has been developed for the treatment of malignancy. DMRIE/DOPE is a cationic lipid that has been shown to facilitate in vitro transfection of plasmid DNA. It has been demonstrated that in vitro transfection with the IL-2 plasmid DNA/DMRIE/DOPE complex results in the expression of sustained levels of biologically active IL-2. Established human tumor cell lines and primary human tumor cells obtained from biopsies are readily transfected in vitro, resulting in the expression of IL-2. Following in vitro transfection, IL-2 expression has been found to persist for up to several weeks in primary tumor cells. In preclinical efficacy studies in a murine model of renal-cell carcinoma the direct intratumoral administration of an IL-2 plasmid DNA/DMRIE/DOPE complex resulted in complete tumor regression in the majority of mice. In preclinical animal-safety studies, repeated administration of Leuvectin was safe and well tolerated. Following these promising preclinical trials, Leuvectin has been taken into clinical trial. The results of two early studies indicate that Leuvectin is safe, is free of systemic toxicity, and has biologic activity.
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PMID:Intratumoral interleukin 2 for renal-cell carcinoma by direct gene transfer of a plasmid DNA/DMRIE/DOPE lipid complex. 1085 52

Leuvectin is a plasmid DNA/lipid complex comprised of a plasmid DNA expression vector (VCL-1102, 30) encoding human interleukin (IL)-2 complexed in a 5:1 mass ratio with DMRIE/DOPE lipid that has been developed for the treatment of cancer. DMRIE/DOPE is a cationic lipid, which facilitates in vitro and in vivo transfection of plasmid DNA. In vitro transfection with the IL-2 plasmid DNA/DMRIE/DOPE complex results in the expression of sustained levels of biologically active IL-2. Human tumor cell lines and primary human tumor cells established from biopsies were readily transfected in vitro resulting in the expression of IL-2. Following in vitro transfection, IL-2 expression continued up to several weeks post-transfection in primary tumor cells. In preclinical efficacy studies in a murine model of renal cell carcinoma (RCC), the direct intratumoral administration of an IL-2 plasmid DNA/DMRIE/DOPE complex resulted in the generation of tumor specific lymphocytes and complete tumor regression in the majority of the mice. In preclinical animal safety studies, repeated administration of Leuvectin was safe and well-tolerated. Following these promising preclinical results, Leuvectin has entered clinical trials and two pilot phase I/II trials are described.
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PMID:Technology evaluation: interleukin-2 gene therapy for the treatment of renal cell carcinoma. 1171 51

Recent data on the application of dendritic cells (DCs) as anti-tumor vaccines has shown their great potential in therapy and prophylaxis of cancer. Here we report on a comparison of two treatment schemes with DCs that display the models of prophylactic and therapeutic vaccination using three different experimental tumor models: namely, Krebs-2 adenocarcinoma (primary tumor), melanoma (B16, metastatic tumor without a primary node) and Lewis lung carcinoma (LLC, metastatic tumor with a primary node). Dendritic cells generated from bone marrow-derived DC precursors and loaded with lysate of tumor cells or transfected with the complexes of total tumor RNA with cationic liposomes were used for vaccination. Lipofectamine 2000 and liposomes consisting of helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and cationic lipid 2D3 (1,26-Bis(1,2-de-O-tetradecyl-rac-glycerol)-7,11,16,20-tetraazahexacosan tetrahydrocloride) were used for RNA transfection. It was shown that DCs loaded with tumor lysate were ineffective in contrast to tumor-derived RNA. Therapeutic vaccination with DCs loaded by lipoplexes RNA/Lipofectamine 2000 was the most efficient for treatment of non-metastatic Krebs-2, where a 1.9-fold tumor growth retardation was observed. Single prophylactic vaccination with DCs loaded by lipoplexes RNA/2D3 was the most efficient to treat highly aggressive metastatic tumors LLC and B16, where 4.7- and 10-fold suppression of the number of lung metastases was observed, respectively. Antimetastatic effect of single prophylactic DC vaccination in metastatic melanoma model was accompanied by the reductions in the levels of Th2-specific cytokines however the change of the levels of Th1/Th2/Th17 master regulators was not found. Failure of double prophylactic vaccination is explained by Th17-response polarization associated with autoimmune and pro-inflammatory reactions. In the case of therapeutic DC vaccine the polarization of Th1-response was found nevertheless the antimetastatic effect was less effective in comparison with prophylactic DC vaccine.
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PMID:Prophylactic Dendritic Cell-Based Vaccines Efficiently Inhibit Metastases in Murine Metastatic Melanoma. 2632 76