Abstract:
:Intratumoral (i.t.) administration of cytokine genes expressed by viral vectors represents a rational approach that induces cytokine secretion at the site they are needed, and i.t. vaccinia virus (VV) has shown promise in mesothelioma patients. However, we and others have shown that the mesothelioma tumor microenvironment includes macrophages, dendritic cells (DCs), and T cells. Therefore, we investigated which of these cell types are infected after exposure to VV or Fowlpox virus (FPV)-cytokine gene constructs. In vitro studies showed that mesothelioma tumor cells were resistant to FPV infection yet highly permissive to infection by VV vectors resulting in significant cytokine production and impaired proliferation. Macrophages secreted low levels of cytokine suggestive of resistance to overt infection. DCs transiently secreted virally derived cytokines, but did not mature during VV infection. VV inhibition of T cell proliferation was rescued by the interleukin (IL)-2 and IL-12 VV constructs. In vivo studies of murine mesotheliomas showed that i.t. injection of the parent VV could not hinder tumor progression. In contrast, the VV-cytokine constructs induced profound tumor regression. These data suggest that i.t. VV-cytokine gene constructs retard tumor growth by infecting mesothelioma cells and targeting the immune system through tumor-infiltrating DC and T cells.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Jackaman C,Nelson DJdoi
10.1038/cgt.2009.85subject
Has Abstractpub_date
2010-06-01 00:00:00pages
429-40issue
6eissn
0929-1903issn
1476-5500pii
cgt200985journal_volume
17pub_type
杂志文章abstract::Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700237
更新日期:2000-10-01 00:00:00
abstract::ING4 as a member of inhibitor of growth (ING) tumor suppressor family has potent inhibitory effects on a variety of tumors. Interleukin-24 (IL-24), a cytokine-tumor suppressor, also shows broad-spectrum and tumor-specific antitumor activities. In this report, we constructed an ING4/IL-24 bicistronic adenovirus (Ad-ING...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.31
更新日期:2011-09-01 00:00:00
abstract::A phase I clinical trial using autologous, IL-7 gene-modified tumor cells in patients with disseminated melanoma has been recently completed. Although no major clinical responses were observed, increased antitumor cytotoxicity was measured in postvaccine peripheral blood lymphocytes in a subset of treated patients. To...
journal_title:Cancer gene therapy
pub_type: 临床试验,杂志文章
doi:10.1038/sj.cgt.7700435
更新日期:2002-03-01 00:00:00
abstract::Screening and identifying molecules target to checkpoint pathways has fostered the development of checkpoint-based anticancer strategies. Among these targets, inhibition of chk2 may induce cell death for tumors whose growth depends on enhanced chk2 activity. However, improvement of the potency and specificity of such ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700967
更新日期:2006-10-01 00:00:00
abstract::Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.4
更新日期:2010-07-01 00:00:00
abstract::A phase l study using intravesical Ad-IFNαSyn3 for patients with bacillus Calmette-Guérin-resistant superficial bladder cancer showed a complete remission (CR) of 43% at 90 days after treatment with high levels of interferon-α (IFNα) being produced. Ad-IFNα kills bladder cancer cells by two apoptotic and one necrotic ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2014.1
更新日期:2014-03-01 00:00:00
abstract::Melanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00274-5
更新日期:2020-12-14 00:00:00
abstract::Recurrent or metastatic cancer in most cases remains an incurable disease, and thus alternative treatment strategies, such as oncolytic virotherapy, are of great interest for clinical application. Oncolytic adenoviruses (Ads) have many advantages as virotherapeutic agents and have been safely employed in the clinics. ...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2012.95
更新日期:2013-02-01 00:00:00
abstract::Angiogenesis is among the most important mechanisms that helps cancer cells to survive, grow and undergo metastasis. Therefore, inhibiting angiogenesis will suppress tumor growth. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are believed to be important players of angiogenesis. The goal of this s...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.76
更新日期:2017-01-01 00:00:00
abstract::Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, ...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41417-020-0174-y
更新日期:2020-12-01 00:00:00
abstract::The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integr...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.64
更新日期:2016-12-01 00:00:00
abstract::We have developed unique replication-competent retroviral (RCR) vectors based on murine leukemia virus that provide improved efficiency of viral delivery, allow for long-term transgene expression and demonstrate an intrinsic selectivity for transduction of rapidly dividing tumor cells. The purpose of this study was to...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7701013
更新日期:2007-03-01 00:00:00
abstract::Immune-isolation of nonautologous cells with microencapsulation protects these cells from graft rejection, thus allowing the same recombinant therapeutic cell line to be implanted in different recipients. This approach was successful in treating HER2/neu-expressing tumors in mice by delivering an interleukin-2 fusion ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700786
更新日期:2005-04-01 00:00:00
abstract::Using our model to grow superficial human bladder cancer in the mouse bladder, we have found that the polyamide compound, Syn3, when injected intravesically for 1 hour at 1 mg/mL on two consecutive days, markedly increases rAd-beta-gal intravesical gene transfer and expression. This enhanced transgene expression was m...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700488
更新日期:2002-08-01 00:00:00
abstract::The ability of viruses to readily infect tumor cells both in vitro and in vivo has resulted in their study as antitumor agents through a variety of strategies. Replicating and conditionally replicating viruses and recombinant viruses encoding genes for toxins and/or prodrugs have been studied for their direct antitumo...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.cgt.7700538
更新日期:2002-12-01 00:00:00
abstract::The antitumor activity of a recombinant canarypox virus expressing wild type murine p53 (ALVAC-p53) was investigated in two murine syngeneic tumors harboring an endogenous p53 mutation (CMS4 and TS/A). Direct intratumor injections of ALVAC-p53 in CMS4 pre-established subcutaneous tumors induced total tumor regression ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700279
更新日期:2001-02-01 00:00:00
abstract::Metastasis is the principal cause of cancer death and occurs through multiple, complex processes. Epithelial to mesenchymal transition (EMT) is an important process during embryonic development and has also been hypothesized to exhibit a significant role in cancer cell invasion and metastasis. MicroRNAs (miRNAs) are a...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2017.1
更新日期:2017-02-01 00:00:00
abstract::Breast cancer is the most common cause of cancer-related death worldwide, thus remaining a crucial health problem among women despite advances in conventional therapy. Therefore, new alternative strategies are needed for effective diagnosis and treatment. One approach is the use of oncolytic viruses for gene-directed ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.49
更新日期:2011-01-01 00:00:00
abstract::To investigate a novel suicide gene for nasopharyngeal carcinoma (NPC) therapy, the yCDglyTK gene was constructed by fusing yeast cytosine deaminase (CD) and herpes simplex type 1 thymidine kinase. The expression of the yCDglyTK gene was detected by RT-PCR and Western blotting, and its bioactivity was demonstrated by ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700728
更新日期:2004-12-01 00:00:00
abstract::Herpes simplex viruses (HSVs) are important pathogens and ideal for gene therapy due to its large genome size. Previous researches on HSVs were hampered because the technology to construct recombinant HSVs were based on DNA homology-dependent repair (HDR) and plaque assay, which are inefficient, laborious, and time-co...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41417-018-0016-3
更新日期:2018-06-01 00:00:00
abstract::Tumor-endothelial interaction contributes to local prostate tumor growth and distant metastasis. In this communication, we designed a novel approach to target both cancer cells and their "crosstalk" with surrounding microvascular endothelium in an experimental hormone refractory human prostate cancer model. We evaluat...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700790
更新日期:2005-03-01 00:00:00
abstract::Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in tumor cells causing direct killing, that is, oncolysis, while sparing normal cells. The oHSVs are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We hypothesized that combining the d...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.75
更新日期:2013-01-01 00:00:00
abstract::Lung cancer is one of the leading causes of death in the world. The underlying cause for lung cancer has been attributed to various factors that include alteration and mutation in the tumor suppressor genes. Restoration of normal function of the tumor suppressor gene is a potential therapeutic strategy. Recent studies...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700756
更新日期:2004-11-01 00:00:00
abstract::Inflammation, among environmental risk factors, is one of the most important contributors to colorectal cancer (CRC) development. In this way, studies revealed that the incidence of CRC in inflammatory bowel disease patients is up to 60% higher than the general population. MicroRNAs (miRNAs), small noncoding RNA molec...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41417-020-0172-0
更新日期:2020-11-01 00:00:00
abstract::Drug metabolizing transgene products, which activate bioreductive cytotoxins, can be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6 transgenes ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700933
更新日期:2006-06-01 00:00:00
abstract::Interleukin-10 (IL-10) is a T helper type 2 (Th2) cytokine that suppresses Th1-mediated, cell-mediated immune responses and reciprocally enhances antibody-mediated responses. Previous studies, however, demonstrated that forced expression of the IL-10 gene in tumor cells could unexpectedly produce antitumor effects. We...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700418
更新日期:2002-01-01 00:00:00
abstract::We exploited the differential activation of hypoxia-inducible factor (HIF)-dependent gene expression in tumors versus normal tissue for the design of a targeted oncolytic herpes simplex virus type-1 (HSV-1). A gene that is essential for viral replication, infected cell polypeptide 4 (ICP4), was placed under the regula...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.62
更新日期:2011-02-01 00:00:00
abstract::Gliomas express a higher amount of Fas than normal brain tissue. It is of interest to know whether expression of the Fas receptor is unfavorable to the antiapoptotic pathways in gliomas. In this study, we introduced the Fas gene via an adenovirus vector (Adeno-Fas) into the A-172, U251, and U-373 MG glioma cell lines,...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700110
更新日期:2000-02-01 00:00:00
abstract::Over the past several years we have obtained considerable evidence indicating that adenoviruses-expressing interferon α (Ad-IFNα) can overcome resistance to the IFNα protein itself. Since cancer cells infected with Ad-IFNα also show high perinuclear cytoplasmic IFNα expression, we were interested in whether endoplasmi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.26
更新日期:2011-09-01 00:00:00
abstract::Replication-competent adenoviruses (Ads) were used for oncolytic virotherapy soon after they were discovered. Recently mutated and genetically engineered Ads have been shown to selectively lyse tumor cells. We have split the human Ad type 5 genome into two defective viruses that complement each other only in certain t...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700001
更新日期:1999-01-01 00:00:00