Abstract:
:The human epidermal growth factor receptors 2, 3, and 4 (HER2, HER3, and HER4, respectively) are frequently overexpressed in many human cancers, and therefore may be potential targets for receptor-mediated gene transfer. To evaluate this possibility, we constructed a series of HER-targeted gene transfer vehicles by covalently linking poly-L-lysine polymers (pLYS) to the epidermal growth factor-like domain of the HER ligand neuregulin-1 (NRG1(177-244)), a HER2 antibody (Ab), and the Fab fragment of the HER2 Ab. In vitro, pLYS modification of NRG1(177-244) decreased the affinity of the ligand for HER3 or HER4 homodimer receptors by 6- to 7-fold. DNA loading of the pLYS-modified NRG1(177-244) had a minimal additional affect on the affinity of the complex for its receptor. In cell lines engineered to solely express HER2, HER3, or HER4, each vehicle correctly targeted the receptors; the NRG1(177-244) construct transferred a luciferase gene only into cells expressing HER4, whereas the HER2 Ab and Fab constructs transferred the reporter gene only into cells expressing HER2. The most efficient gene transfer occurred using the intact HER2 Ab as a gene transfer vehicle, whereas the Fab fragment of the HER2 Ab was the least efficient, and NRG1(177-244) was intermediate. These studies suggest that the NRG receptor or HER2, a component of the receptor, can be pursued as targets for gene transfer.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Kern JA,Wakita R,Sliwkowski MXdoi
10.1038/sj.cgt.7700069subject
Has Abstractpub_date
1999-11-01 00:00:00pages
537-45issue
6eissn
0929-1903issn
1476-5500journal_volume
6pub_type
杂志文章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::Direct intratumoral injection of a lipid/DNA complex encoding an allogeneic major histocompatibility complex (MHC) class I molecule leads to regression of both an immunogenic murine tumor and also melanoma lesions in some patients. We have sought to understand the mechanism(s) for this augmentation of antitumor activi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) have affinity to tumor sites where they home, affecting their biology and growth. Previously, we have isolated mesenchymal cells from the decidua of the human placenta named as decidua-derived MSCs (DMSCs). The aims of the present study were to investigate the migration capacity of DMSCs ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.71
更新日期:2013-01-01 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::The aim of the present study is to identify the optimal anticancer agents for use in combination with gene therapy using wild-type (wt) p53 gene transfer. We used adenoviral vectors expressing human wt p53 (AdCAp53) and investigated the effects of wt p53 gene transfer in combination with 12 anticancer agents on a huma...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700096
更新日期:2000-02-01 00:00:00
abstract::Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00253-w
更新日期:2020-11-30 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::Arming oncolytic adenoviral vectors with anticancer transgenes that can be expressed in a tumor-selective manner may enable the engineering of vectors with increased potency, while retaining their safety profile. Armed oncolytic adenoviral vectors were constructed in which transgene expression has been linked via modi...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7701093
更新日期:2008-01-01 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::B-cell malignancies upregulate the B-cell lymphoma 2 (Bcl-2) family inhibitors of the intrinsic apoptosis pathway, making them therapy resistant. However, small-molecule inhibitors of Bcl-2 family members such as ABT-737 restore a functional apoptosis pathway in cancer cells, and its oral analog ABT-263 (Navitoclax) h...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.35
更新日期:2013-07-01 00:00:00
abstract::Cancer gene therapy approaches are often designed as single-agent treatments; however, greater therapeutic effect might be obtained if combined with an established conventional treatment regimen such as chemotherapy. In this context, conditional promoters are useful tools, because they may be induced by therapeutic mo...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700196
更新日期:2000-06-01 00:00:00
abstract::RNA interference (RNAi) is a natural cellular regulatory process that inhibits gene expression by transcriptional, post-transcriptional and translational mechanisms. Synthetic approaches that emulate this process (small interfering RNA (siRNA), short hairpin RNA (shRNA)) have been shown to be similarly effective in th...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.35
更新日期:2010-11-01 00:00:00
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 ce...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700995
更新日期:2007-01-01 00:00:00
abstract::A nonviral gene delivery vector has been developed in our laboratory based on the cationic polymer, poly(2-(dimethylethylamino)ethyl methacrylate) (p(DMAEMA)). p(DMAEMA)-based polyplexes have been successfully used for the transfection of OVCAR-3 cells in vitro. However, these polyplexes were unable to transfect OVCAR...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700311
更新日期:2001-06-01 00:00:00
abstract::Cancer is one of the main problems in public health worldwide. Despite rapid advances in the diagnosis and treatment of cancer, the efficacy of current treatment strategies is still limited. There are promising new results in animal models whereby mesenchymal stem cells (MSCs) can be used as vehicles for targeted ther...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2016.35
更新日期:2016-09-01 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::Cationic liposomes have been shown to potentiate markedly the ability of plasmid DNA to activate innate immune responses. We reasoned therefore that liposome-DNA complexes (LDC) could be used to produce more effective plasmid DNA vaccines for cancer. To test this hypothesis, tumor-bearing mice were vaccinated with con...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700982
更新日期:2006-11-01 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::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
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::Thymidylate synthase (TS) catalyzes de novo production of thymidylate for DNA synthesis and cell proliferation. As such, TS has been a target of antitumor chemotherapy for many years. Our laboratory has identified several antisense oligodeoxynucleotides (ODNs) that downregulate TS mRNA and protein, inhibit cell prolif...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700566
更新日期:2003-04-01 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::Oncolytic reovirus administration has been well tolerated by cancer patients in clinical trials. However, its anti-cancer efficacy as a monotherapy remains to be augmented. We and others have previously demonstrated the feasibility of producing replication-competent reoviruses expressing a heterologous transgene. Here...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-018-0063-9
更新日期:2019-09-01 00:00:00
abstract::Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker for the colorectal cancer (CRC). It plays critical roles in the oncogenesis, progression, and metastasis of CRC. DCLK1 can be an intriguing therapeutic target for CRC treatment. However, the molecular mechanism of how DCLK1 functions is unclear currently....
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0144-4
更新日期:2020-09-01 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::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::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::The use of prodrug-activated ("suicide") gene therapy has been shown to be effective in inducing tumor regression when only a small proportion of tumor cells contains the suicide gene. These experiments were designed to test whether additional therapeutic benefit may be obtained by stimulating the immune response. Mur...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700259
更新日期:2000-12-01 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::We tested three hammerhead ribozymes for their ability to bind and cleave RNA transcripts derived from the E6 and E7 genes of human papillomavirus (HPV) type-18. Targets were located at nucleotides (nt) 123, 309, and 671 of the viral transcript. In vitro each ribozyme hybridized to its target site when the ribozyme:ta...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00