Abstract:
:CD4+CD25+regulatory T cells (T(reg)) impair anti-tumor and anti-viral immunity. As there are higher T(reg) levels in cancer patients compared with healthy individuals, there is considerable interest in eliminating them or altering their function as part of cancer or viral immunotherapy strategies. The scurfin transcriptional regulator encoded by the member of the forkhead winged helix protein family (FOXP3) is critical for maintaining the functions of T(reg). We hypothesized that targeting FOXP3 expression with a novel arginine-rich, cell-penetrating, peptide-conjugated phosphorodiamidate morpholino (PPMO) based antisense would eliminate T(reg) and enhance the induction of effector T-cell responses. We observed that the PPMO was taken up by activated T cells in vitro and could downregulate FOXP3 expression, which otherwise increases during antigen-specific T-cell activation. Generation of antigen-specific T cells in response to peptide stimulation was enhanced by pre-treatment of peripheral blood mononuclear cells with the FOXP3-targeted PPMO. In summary, modulation of T(reg) levels using the FOXP3 PPMO antisense-based genomic strategy has the potential to optimize immunotherapy strategies in cancer and viral immunotherapy.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Morse MA,Hobeika A,Serra D,Aird K,McKinney M,Aldrich A,Clay T,Mourich D,Lyerly HK,Iversen PL,Devi GRdoi
10.1038/cgt.2011.63subject
Has Abstractpub_date
2012-01-01 00:00:00pages
30-7issue
1eissn
0929-1903issn
1476-5500pii
cgt201163journal_volume
19pub_type
杂志文章abstract::Chimeric Antigen Receptor (CAR) T-cell therapy, as an approved treatment option for patients with B cell malignancies, demonstrates that genetic modification of autologous immune cells is an effective anti-cancer regimen. Erythropoietin-producing Hepatocellular receptor tyrosine kinase class A2 (EphA2) is a tumour ass...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00221-4
更新日期:2020-09-01 00:00:00
abstract::Typically, gene transfer strategies utilize a promoter/transgene arrangement that treat these elements independently and do not offer any interplay between them. Our goal was to establish a promoter/transgene combination that would result in improvement in both expression and therapeutic effect by utilizing the transc...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700846
更新日期:2005-12-01 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::Ad-PPE-Fas-c is an adenovector that expresses Fas-c under the control of the modified pre-proendothelin-1 (PPE-1) promoter. Fas-c is a chimeric death receptor containing the extracellular portion of tumour necrosis factor 1 receptor (TNFR1) and the transmembrane and intracellular portion of Fas. We recently demonstrat...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2008.20
更新日期:2008-08-01 00:00:00
abstract::The DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) is epigenetically silenced in some tumors by MGMT gene promoter methylation. MGMT-hypermethylated solid tumors have enhanced susceptibility to the cytotoxic effects of alkylating chemotherapy such as temozolomide, compared with non-methylated tumors. ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2017.27
更新日期:2017-08-01 00:00:00
abstract::Oncolytic viruses (OVs) have shown great anti-cancer potential in animal models, but only modest success in early clinical trials. A better understanding of the mechanisms underlining OV efficacy is needed to resolve this discrepancy. In the clinic, OV therapy will likely be combined with traditional chemotherapy, und...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.33
更新日期:2012-08-01 00:00:00
abstract::The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatm...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700331
更新日期:2001-07-01 00:00:00
abstract::The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancer...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700226
更新日期:2000-09-01 00:00:00
abstract::Retroviral replicating vectors (RRVs) have achieved efficient tumor transduction and enhanced therapeutic benefit in a wide variety of cancer models. Here, we evaluated two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), which utilize different cellular recept...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-018-0037-y
更新日期:2019-02-01 00:00:00
abstract::We aimed to analyze the association between the distribution of dendritic cells (DC) with expression of tumor-infiltrating T lymphocytes and clinicopathologic parameters with prognosis in epithelial ovarian cancer (EOC). Thirty-three EOC patient samples were surgically resected, and pathology was examined for clinicop...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2015.7
更新日期:2015-03-01 00:00:00
abstract::To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2015.37
更新日期:2015-08-01 00:00:00
abstract::In this article we describe an improved method to produce a conjugate of anti-erythrocyte growth factor (EGF) receptor monoclonal antibody with polylysine via thio-ether bonds. The resulting antibody/polylysine conjugate was found to be a much more stable DNA (gene) carrier than the previous conjugate formed via disul...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Gastric cancer (GC) is a common cancer and a leading cause of cancer-related deaths worldwide. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in GC progression. This study identified functional significance of X inactive specific transcript (XIST) in GC. The expression of XIST and E...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00220-5
更新日期:2020-11-16 00:00:00
abstract::Oncolytic virotherapy has shown substantial promises as an alternative therapeutic modality for solid tumors in both preclinical studies and clinical trials. The main therapeutic activity of virotherapy derives from the direct lytic effect associated with virus replication and the induction of host immune responses to...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.46
更新日期:2011-11-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) recurrence is one of the leading causes of death after orthotopic liver transplantation (OLT). The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex, which has an indispensable role in innate and acquired ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.7
更新日期:2016-06-01 00:00:00
abstract::Specificity is a prerequisite for systemic gene therapy of hepatocarcinoma. In vitro, the tumor-specific viral death effector Apoptin selectively induces apoptosis in malignant hepatic cells. Intratumoral treatment of xenografted subcutaneous hepatomas with Apoptin results in tumor regression. Here, we report a system...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700985
更新日期:2007-01-01 00:00:00
abstract::This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG gro...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2017.13
更新日期:2017-06-01 00:00:00
abstract::Heat shock proteins (hsps) chaperone cytosolic peptides, forming complexes that stimulate antitumor immunity. Hsps facilitate signal 1 in the two-signal model of T-cell costimulation, whereas cell adhesion molecules such as B7.1 provide secondary (signal 2) costimulatory signals. B7.1 gene transfer into tumors in situ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700395
更新日期:2001-12-01 00:00:00
abstract::We have used the tetracycline (tet)-regulated system as described previously to evaluate the applicability of controlled gene expression in cancer gene therapy. As a model gene, we used the human interleukin-2 (IL-2) gene, which has been placed under the transcriptional control of the tetO/promoter. Human melanoma cel...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700021
更新日期:1999-03-01 00:00:00
abstract::The rapid development of both knowledge and techniques in molecular biology have made it possible to engineer genetic constructs and transfer them into cells of individuals with various diseases. Such gene therapies may alleviate or perhaps even cure diseases for which no adequate treatment now exists. One potential a...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:
更新日期:1995-06-01 00:00:00
abstract::MicroRNAs (miRNAs) were discovered more than a decade ago as noncoding, single-stranded small RNAs (approximately 22 nucleotides) that control the timed gene expression pattern in Caenorhabditis elegans life cycle. A number of these evolutionarily conserved, endogenous miRNAs have been shown to regulate mammalian cell...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2008.8
更新日期:2008-06-01 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::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::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::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::Melanoma incidence is growing at a faster rate than any other human malignancy. Wild-type (wt) p53 is important in both G(1) and G(2) cell cycle arrest, and cyclin D1 (CD1) is necessary for G(1)-->S progression in melanoma cells. We reported that an adenoviral vector containing wt p53 significantly reduced [(3)H]thymi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700492
更新日期:2002-10-01 00:00:00
abstract::Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0110-1
更新日期:2020-05-01 00:00:00
abstract::We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-ma...
journal_title:Cancer gene therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/cgt.2012.72
更新日期:2012-12-01 00:00:00
abstract::Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene gamma(1)34.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700890
更新日期:2006-03-01 00:00:00
abstract::We have examined the effect of adenoviruses expressing soluble transforming growth factor receptorII-Fc (sTGFβRIIFc) in a 4T1 mouse mammary tumor bone metastasis model using syngeneic BALB/c mice. Infection of 4T1 cells with a non-replicating adenovirus, Ad(E1-).sTβRFc, or with two oncolytic adenoviruses, Ad.sTβRFc an...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.41
更新日期:2012-09-01 00:00:00