Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, several studies have shown that vaccine therapy using dendritic cells (DCs) genetically engineered to express a surrogate tumor antigen can effectively induce antitumor immunity. In this study, murine bone marrow DCs were adenovirally transduced with murine endogenous tumor antigen gp70 expressed in CT26 cells and granulocyte macrophage colony-stimulating factor (GM-CSF), and we examined whether antigen-specific CTL responses and therapeutic immunity could be induced in mice immunized with those genetically modified DCs. The cytotoxic activity against CT26 in mice immunized with gp70-transduced DCs was significantly higher than that in control (P < 0.01) and was enhanced by GM-CSF-cotransduction (P < 0.001). GM-CSF gene transfer into DCs expressing tumor-associated antigen enhances CC chemokine receptor 7 expression on DCs, leading to improved migratory capacity of DCs to draining lymph nodes. Consequently, an effective antitumor immune response would be induced. Vaccination using gp70-transduced DCs provided remarkable therapeutic efficacy in s.c. models. Moreover, it could be sufficiently augmented by GM-CSF-cotransduction of DCs. These results support that vaccination therapy using DCs simultaneously transduced with tumor-associated antigen can elicit potent CTL response, and GM-CSF-cotransduction of DCs could optimize therapeutic response. Further investigation is needed to optimize this vaccine therapy to achieve the obvious benefit in clinical application.
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PMID:Dendritic cells genetically engineered to simultaneously express endogenous tumor antigen and granulocyte macrophage colony-stimulating factor elicit potent therapeutic antitumor immunity. 1217 8

Several studies have shown that vaccine therapy using dendritic cells (DCs) pulsed with specific tumor antigen peptides can effectively induce antitumor immunity. Peptide-pulsed DC therapy is reported to be effective against melanoma, while it is still not sufficient to show the antitumor therapeutic effect against epithelial solid tumors such as gastrointestinal malignancies. Recently, it has been reported that vaccine therapy using DCs transduced with a surrogate tumor antigen gene can elicit a potent therapeutic antitumor immunity. In this study, we investigated the efficacy of vaccine therapy using DCs transduced with the natural tumor antigen in comparison with peptide-pulsed DCs. DCs derived from murine bone marrow were adenovirally transduced with murine endogenous tumor antigen gp70 gene, which is expressed in CT26 cells, or DCs were pulsed with the immunodominant peptide AH-1 derived from gp70. We compared these two cancer vaccines in terms of induction of antigen-specific cytotoxic T lymphocyte (CTL) responses, CD4+ T cell response against tumor cells, migratory capacity of DCs and therapeutic immunity in vivo. The cytotoxic activity of splenocytes against CT26 and Meth-A pulsed with AH-1 in mice immunized with gp70 gene-transduced DCs was higher than that with AH-1-pulsed DCs. CD4+ T cells induced from mice immunized with gp70 gene-transduced DCs produced higher levels of IFN-gamma by stimulation with CT26 than those from mice immunized with AH-1-pulsed DCs (p < 0.0001), and it was suggested that DCs transduced with tumor-associated antigen (TAA) gene induced tumor-specific CD4+ T cells, and those CD4+ T cells played a critical role in the priming phase of the CD8+ T cell response for the induction of CD8+ CTL. Furthermore, DCs adenovirally transduced with TAA gene showed an enhancement of expression of CC chemokine receptor 7 and improved the migratory capacity to draining lymph nodes. In subcutaneous models, the vaccination using gp70 gene-transduced DCs provided a remarkably higher therapeutic efficacy than that using AH-1-pulsed DCs. These results suggested that vaccine therapy using DCs adenovirally transduced with TAA gene can elicit potent antitumor immunity, and may be useful for clinical application.
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PMID:Dendritic cells transduced with tumor-associated antigen gene elicit potent therapeutic antitumor immunity: comparison with immunodominant peptide-pulsed DCs. 1600 53

Tongue squamous cell carcinoma (TSCC) is a malignant tumor. Long noncoding RNAs (lncRNAs) have been proved to be involved in the regulation of the progression of various cancers. However, the mechanism of lncRNA urothelial cancer-associated 1 (UCA1) in the progression of TSCC remains unclear. The expression levels of UCA1, microRNA-138-5p (miR-138-5p), and CC chemokine receptor 7 (CCR7) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion were detected using colony formation assay and transwell assay, respectively. Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related proteins and CCR7 protein. Moreover, the extracellular acidification rate (ECAR) of cells was measured by the Seahorse XF Extracellular Flux Analyzer, and the adenosine triphosphate (ATP) level, glucose uptake, and lactate produce of cells were tested by their corresponding assay kits. Further, the dual-luciferase reporter assay was used to confirm the interaction between miR-138-5p and UCA1 or CCR7. In addition, the effect of UCA1 on TSCC tumor growth in vivo was evaluated by animal experiments. We found that UCA1 and CCR7 were upregulated, while miR-138-5p was downregulated in TSCC tissues. Silenced UCA1 restrained the proliferation, migration, invasion, and glycolysis metabolism of TSCC cells. Similarly, knockdown of CCR7 also could suppress the progression of TSCC. Besides, UCA1 overexpression promoted TSCC progression, while this promotion effect could be reversed by CCR7 silencing. miR-138-5p could be sponged by UCA1 and could target CCR7. Additionally, miR-138-5p overexpression could reverse the promotion effect of overexpressed UCA1 on TSCC progression. Furthermore, the UCA1 knockdown reduced TSCC tumor growth in vivo. In conclusion, lncRNA UCA1 might function as an oncogene in TSCC through regulating the miR-138-5p/CCR7 axis, providing a new biomarker for TSCC treatment.
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PMID:Long noncoding RNA UCA1 regulates CCR7 expression to promote tongue squamous cell carcinoma progression by sponging miR-138-5p. 3274 49