UMLS:C0038362 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0038362 (stomatitis)
8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new retroviral system has been developed for the generation of a cDNA library and the functional cloning of tumor antigens. These retroviral vectors contain a cytomegalovirus promoter in the 5' long terminal repeat, an extended packaging signal for rapid production of high-titer retroviral particles, and many convenient cloning sites for cDNA library construction. The vesicular stomatitis virus G protein has been used to generate pseudotype retroviral particles to enable efficient viral infection. Using this system, viral titers in the range of 10(6) colony-forming units/ml could be generated routinely, and a high transduction efficiency in human primary cells, including fibroblasts, was achieved. In addition, a new procedure has been devised for screening a retrovirus-based cDNA library without a functional selection. The utility of this system was demonstrated by constructing a retrovirus-based cDNA library and re-isolating the NY-ESO-1 tumor antigen from a cDNA library using an antigen-specific CTL. This approach can facilitate the identification of novel tumor antigens recognized by T cells without knowledge of MHC class I restriction elements and is generally applicable for the isolation of any gene as long as a biological assay is available.
...
PMID:Development of a retrovirus-based complementary DNA expression system for the cloning of tumor antigens. 972 52

Tumor-specific genes delivered to dendritic cells (DCs) have been used for the generation of cytotoxic T cells (CTLs), but their application has been limited on the one hand by low viral titers resulting in low transduction efficiency and poor protein production, and on the other hand by immunogenicity of the selectable marker and poor viability of the DCs. We addressed these limitations by creating a multipurpose master vector (pMV) and cloning the tumor gene NY-ESO-1, which is highly expressed in more than 50% of advanced myeloma patients. pMV was constructed from a Moloney murine leukemia virus (Mo-MuLV)-based retroviral backbone with the following features: (1) an extended packaging signal to achieve high viral titers, (2) a splice acceptor region to facilitate protein production, (3) a nonimmunogenic selectable marker, dihydrofolate reductase-L22Y (DHFR(L22Y)), to exclude the generation of CTLs against the selectable marker, (4) an internal ribosomal entry site between the tumor-specific gene (NY-ESO-1) and the selectable marker DHFR(L22Y) for coexpression of two heterologous gene products from a single bicistronic mRNA, minimizing the possibility of differential expression of these two genes, and (5) human granulocyte-macrophage colony-stimulating factor (hGM-CSF) cDNA driven by the human T-lymphotropic virus promoter to enhance DC function and viability. Recombinant virus of pMV-NY-ESO-1 was generated with vesicular stomatitis virus G envelope protein (VSV-G) in the GP2-293 cell line for efficient transduction. We present evidence that the DC phenotype is unaltered after transduction and that more than 85% of DCs express NY-ESO-1, which secrete approximately 40 ng of GM-CSF per 10(6) DCs.
...
PMID:High-level expression of cancer/testis antigen NY-ESO-1 and human granulocyte-macrophage colony-stimulating factor in dendritic cells with a bicistronic retroviral vector. 1450 68

Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumor-associated antigens (TAA) and danger signals from the dying infected tumor cells. In this study, we sought to determine if the lysis of tumor cells induced by different OV: measles virus, vaccinia virus, vesicular stomatitis virus, herpes simplex type I virus, adenovirus or enterovirus, has consequences on the capacity of tumor cells to present TAA, such as NY-ESO-1. We show that the co-culture of NY-ESO-1^neg/HLA-DP4^pos melanoma cells with NY-ESO-1^pos/HLA-DP4^neg melanoma cells infected and killed by different OV induces an intercellular transfer of NY-ESO-1 that allows the recognition of NY-ESO-1^neg/HLA-DP4^pos tumor cells by an HLA-DP4/NY-ESO-1_(157-170)-specific CD4+ cytotoxic T cell clone, NY67. We then confirmed this result in a second model with an HLA-DP4+ melanoma cell line that expresses a low amount of NY-ESO-1. Recognition of this cell line by the NY67 clone is largely increased in the presence of OV productive infection. Altogether, our results show for the first time another mechanism of stimulation of the anti-tumor immune response by OV, via the loading of tumor cells with TAA that sensitizes them for direct recognition by specific effector CD4+ T cells, supporting the use of OV for cancer immunotherapy.
...
PMID:Oncolytic viruses sensitize human tumor cells for NY-ESO-1 tumor antigen recognition by CD4+ effector T cells. 2939 8