Abstract：
:The success of cancer gene therapies requiring in vivo gene transfer is severely hampered by the low efficacy of gene transfer, which has been difficult to improve. We therefore established a novel strategy to increase the share of transduced cells post gene transfer. We hypothesized that in vivo selection of tumor cells transduced with a suicide gene effectively enriches these cells within a tumor, thus allowing for an increased bystander effect after the prodrug is given, leading to enhanced eradication of tumor cells. We reasoned that in vivo enrichment should be achieved by exploiting the metabolism of the suicide gene product. For this 'enrichment-eradication' strategy we chose a fusion gene of cytosine deaminase and uracil phosphoribosyl transferase. Positive selection (enrichment) was to be achieved by concurrently giving N-(phosphonacetyl)-L-aspartate, an inhibitor of pyrimidine de novo synthesis, which leads to pyrimidine depletion-mediated death of non-transduced cells, and cytosine, to rescue fusion gene expressing cells via the pyrimidine salvage pathway. Negative selection (eradication) was to be induced by giving the prodrug 5-fluorocytosine. Indeed, murine NXS2 neuroblastoma cells transduced with the fusion gene were effectively enriched in vitro, leading to a near-complete bystander effect. In vivo enrichment-eradication of NXS2 cells led to decreased tumor growth. This proof-of-principle study shows that enrichment-eradication may compensate the effects of low in vivo gene transfer efficacy, a major obstacle in cancer gene therapy.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Unger MM,Wahl J,Ushmorov A,Buechele B,Simmet T,Debatin KM,Beltinger Cdoi
10.1038/sj.cgt.7700995subject
Has Abstractpub_date
2007-01-01 00:00:00pages
30-8issue
1eissn
0929-1903issn
1476-5500pii
7700995journal_volume
14pub_type
杂志文章abstract：:p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was c...
journal_title：Cancer gene therapy
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/sj.cgt.7700214
更新日期：2000-07-01 00:00:00
abstract：:Cis-diamminedichloroplatinum(II) increased in vivo lipofection efficiency of tumor cells with a target gene, interferon gamma (IFN gamma), in a murine metastatic ovarian carcinoma model. The expression of IFN gamma gene in ascitic tumors reached a peak at day 11 after cisplatin treatment and lasted over 1 week. A loca...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：:Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the γ3...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2017.33
更新日期：2017-09-01 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 Ki-ras gene is frequently mutated and/or overexpressed in human cancer. Since it is suspected to play a key role in the pathogenesis of many tumors, there is interest to search for strategies aiming at the specific inhibition of this oncogene. In this paper, we investigated the capacity of a 20 mer G-rich oligonuc...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700722
更新日期：2004-07-01 00:00:00
abstract：:Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It is still unclear if and how miRNAs-221/222 are implicated in breast cancer and the resistance to estrogen receptor modulator tamoxifen. We investigated the roles and mechanisms of miR-221/222 in breast cancer cells, particularly in modula...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2014.29
更新日期：2014-07-01 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：BACKGROUND:Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral inject...
journal_title：Cancer gene therapy
pub_type： 临床试验,杂志文章
doi：10.1038/sj.cgt.7700019
更新日期：1999-07-01 00:00:00
abstract：:The gene transfer of tumor-specific chimeric immunoglobulin T-cell receptors (cIgTCRs) combining antibody-like specificity with the effector cell function could be an attractive tool in immunotherapy. In this study, we directed the human natural killer (NK) cell line YT to tumor cells by gene transfer of a cIgTCR with...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700453
更新日期：2002-04-01 00:00:00
abstract：:Colon carcinoma accounts for 20% of deaths due to malignancies in the Western world. Once metastases occur, therapeutic options are limited, with an approximate 5-year survival of only 5%. To investigate the potential of new gene therapeutic approaches, a hepatic micrometastasis model of colon carcinoma in BALB/c mice...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700131
更新日期：2000-03-01 00:00:00
abstract：:Survivin is expressed in most cancers but is undetectable in differentiated adult cells, and plays an important role both in the suppression of apoptosis and mitotic spindle checkpoint; thus it has attracted great interest as a potential drug target. In this study, we investigated the antigene and antiproliferative ef...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700581
更新日期：2003-05-01 00:00:00
abstract：:Most cancer vaccines to date have made use of common tumor antigens or allogenic cancer cell lines. The majority of tumor antigens may, however, be unique patient-specific antigens. Dendritic cells (DCs) are the most potent antigen-presenting cells known. The present report is a full-scale preclinical evaluation of au...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700837
更新日期：2005-06-01 00:00:00
abstract：:Circular RNAs (circRNAs) are involved in the regulation of many pathophysiological processes as non-coding RNAs. This study focuses on the role of circRACGAP1 in the development of non-small cell lung cancer (NSCLC). Expression patterns of circRACGAP1 and miR-144-5p in NSCLC tissues and cell lines were quantified by q...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-020-00209-0
更新日期：2020-08-11 00:00:00
abstract：:Adenoviral technology has been thoroughly evaluated for delivering genetic material to tumor tissue and the surrounding microenvironment. Almost any gene can be cloned into an adenovirus (Ad) vector, which when combined with strong, constitutively active promoters permit up to a million-fold amplification of the trans...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2012.16
更新日期：2012-07-01 00:00:00
abstract：:Cisplatin (DDP)-based strategies are the first-line treatment for cancers; however, resistance to DDP remains a major obstacle to cancer treatment. The current study set out to investigate the effects of microRNA-181c (miR-181c) on the resistance of ovarian cancer cells to DDP. Ovarian cancer-associated miRs as well a...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-020-0195-6
更新日期：2020-07-07 00:00:00
abstract：:Although early stage cholangiocarcinoma (CC) can be cured by surgical extirpation, the options for treatment of advanced stage CC are very few and suboptimal. Oncolytic virotherapy using replication-competent vaccinia virus (VACV) is a promising new strategy to treat human cancers. The ability of oncolytic VACV GLV-1h...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2015.60
更新日期：2015-12-01 00:00:00
abstract：:Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We created a recombinant replicating VSV (rrVSV) that preferentially infected Her2/neu expressing breast cancer cells. We now used this rrVSV to treat macroscopic peritoneal tumor implants of a mouse mammary tumor cell line stably transfected to e...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2008.55
更新日期：2009-01-01 00:00:00
abstract：:Salmonella typhimurium (hereafter S. typhimurium), as Gram-negative facultative anaerobic bacteria, are good candidates for cancer therapy and delivering therapeutic antitumor agents. However, it is necessary to reduce the virulence of such bacteria and enhance their tumor-targeting ability, and their immunostimulator...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-018-0021-6
更新日期：2018-08-01 00:00:00
abstract：:Prostate cancer is one of the most commonly diagnosed cancers and the second leading cause of cancer deaths in Americans. The high mortality rate is mainly attributed to the invasiveness and metastasis of advanced prostate cancer. Targeting the molecules involved in metastasis could be an effective mode of treatment f...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2010.16
更新日期：2010-09-01 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：: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：:To improve the expression levels of transgenes in malignant hematopoietic cells, we developed a novel adenoviral-alphavirus hybrid vector Ad5/F11p-SFV-GFP that contains a Semliki Forest Virus (SFV) replicon and chimeric fibers of Ad5 and Ad11p. Ad5/F11p-SFV-GFP infected >95% of K562, U937 or Jurkat cells and 23.65% of...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2013.37
更新日期：2013-08-01 00:00:00
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：:We previously developed the "immunogene" approach toward cancer gene therapy using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we describe an improved immunogene system, in which the antigen-binding (Fab) fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were conjugated with...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：
更新日期：1998-11-01 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：:MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. In this study, we investigate whether let-7b acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. We analyzed the expression of let-7b in 60 pair-matched gastric neoplastic and adjacent ...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/cgt.2014.75
更新日期：2015-04-01 00:00:00
abstract：:Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/sj.cgt.7700938
更新日期：2006-06-01 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：:Gastric cancer is the fourth most common type of cancer. Liver-intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the...
journal_title：Cancer gene therapy
pub_type： 杂志文章
doi：10.1038/s41417-017-0001-2
更新日期：2018-02-01 00:00:00
abstract：:The immune responses of 10 patients with advanced non-small cell lung cancer receiving monthly intratumoral injections of a recombinant adenovirus containing human wild-type p53 (Ad-p53) to adenovirus and transgene antigens were studied. The predominate cellular and humoral immune responses as measured by lymphocyte p...
journal_title：Cancer gene therapy
pub_type： 临床试验,杂志文章
doi：10.1038/sj.cgt.7700138
更新日期：2000-04-01 00:00:00
