Oncolytic adenovirus-mediated transfer of the antisense chk2 selectively inhibits tumor growth in vitro and in vivo.

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 therapeutics remains a major challenge. To resolve this problem, we constructed M3, a novel recombinant adenovirus with a 27-bp deletion in E1A CR2 region by which to realize tumor-specific replication, and an 829-bp of antisense chk2 fragment inserted into the E3 coding region. In this design, M3 exploited the native adenovirus E3 promoters to express antisense chk2 cDNA in a viral replication-dependent fashion, and preferentially silenced the chk2 gene in tumor cells. In vitro and in vivo assays confirmed that downregulated chk2 expression induced by M3 infection was tumor-specific and virus replication-dependent. Furthermore, systemic administration of M3 combined with a low dose of cisplatin cured 75% (9/12) of orthotopic hepatic carcinoma mouse models that were otherwise resistant to cisplatin. Our results indicated that the upcoming development in this field would improve the antitumor efficacy and maximize the synergistic effect of oncolytic viruses administered with traditional chemotherapy or radiotherapy.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Chen G,Zhou J,Gao Q,Huang X,Li K,Zhuang L,Huang M,Xu G,Wang S,Lu Y,Ma D

doi

10.1038/sj.cgt.7700967

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

930-9

issue

10

eissn

0929-1903

issn

1476-5500

pii

7700967

journal_volume

13

pub_type

杂志文章
  • Improved gene transfer selectivity to hepatocarcinoma cells by retrovirus vector displaying single-chain variable fragment antibody against c-Met.

    abstract::Engineered retroviruses are widely used vectors for cancer gene therapy approaches. However, the ability to target cells of therapeutic interest while controlling the expression of the transferred genes would improve both the efficiency and the safety of viral vectors. In this study, we investigated the ability of a r...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700640

    authors: Nguyen TH,Loux N,Dagher I,Vons C,Carey K,Briand P,Hadchouel M,Franco D,Jouanneau J,Schwall R,Weber A

    更新日期:2003-11-01 00:00:00

  • Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers.

    abstract::Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cel...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.38

    authors: Chang JT,Kuo TF,Chen YJ,Chiu CC,Lu YC,Li HF,Shen CR,Cheng AJ

    更新日期:2010-12-01 00:00:00

  • Enhancing the cytotoxicity of chemoradiation with radiation-guided delivery of anti-MGMT morpholino oligonucleotides in non-methylated solid tumors.

    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

    authors: Ambady P,Wu YJ,Walker JM,Kersch C,Pagel MA,Woltjer RL,Fu R,Muldoon LL,Neuwelt EA

    更新日期:2017-08-01 00:00:00

  • Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21.

    abstract::Mammary carcinomas that develop in C3 (1)/SV40 T- antigen (TAg) transgenic mice have lost the p53-mediated induction of p21, leading to increased cellular proliferation and significant elevations of cyclins and Cdks. To test whether p21 could serve as a target for anticancer therapy for this mammary cancer model, a re...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700275

    authors: Shibata MA,Yoshidome K,Shibata E,Jorcyk CL,Green JE

    更新日期:2001-01-01 00:00:00

  • The effects of radiation on antitumor efficacy of an oncolytic adenovirus vector in the Syrian hamster model.

    abstract::We report that radiation enhances the antitumor efficacy of the oncolytic adenovirus vector VRX-007 in Syrian hamster tumors. We used tumor-specific irradiation of subcutaneous tumors and compared treatment options of radiation alone or combined with VRX-007 and cyclophosphamide (CP). Radiation therapy further augment...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2013.50

    authors: Young BA,Spencer JF,Ying B,Toth K,Wold WS

    更新日期:2013-09-01 00:00:00

  • MicroRNA binding site polymorphism in inflammatory genes associated with colorectal cancer: literature review and bioinformatics analysis.

    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

    authors: Karimzadeh MR,Zarin M,Ehtesham N,Khosravi S,Soosanabadi M,Mosallaei M,Pourdavoud P

    更新日期:2020-11-01 00:00:00

  • Blood outgrowth endothelial cell-based systemic delivery of antiangiogenic gene therapy for solid tumors.

    abstract::Endothelial cells and endothelial cell precursors encoding a therapeutic gene have induced antitumor responses in preclinical models. Culture of peripheral blood provides a rich supply of autologous, highly proliferative endothelial cells, also referred to as blood outgrowth endothelial cells (BOECs). The aim of this ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.42

    authors: Bodempudi V,Ohlfest JR,Terai K,Zamora EA,Vogel RI,Gupta K,Hebbel RP,Dudek AZ

    更新日期:2010-12-01 00:00:00

  • CRISPR/Cas9 genome editing technology significantly accelerated herpes simplex virus research.

    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

    authors: Wang D,Wang XW,Peng XC,Xiang Y,Song SB,Wang YY,Chen L,Xin VW,Lyu YN,Ji J,Ma ZW,Li CB,Xin HW

    更新日期:2018-06-01 00:00:00

  • Oncolytic adenovirus retargeted to Delta-EGFR induces selective antiglioma activity.

    abstract::The fact that glioblastomas, which are one of the most devastating cancers, frequently express the Delta-EGFR (epithelial growth factor receptor) also called mutant variant III of EGFR (EGFRvIII) suggests that this cancer cell-specific receptor might serve as an ideal target for cancer therapy. To assess its potential...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2008.75

    authors: Piao Y,Jiang H,Alemany R,Krasnykh V,Marini FC,Xu J,Alonso MM,Conrad CA,Aldape KD,Gomez-Manzano C,Fueyo J

    更新日期:2009-03-01 00:00:00

  • Targeting HSV-1 virions for specific binding to epidermal growth factor receptor-vIII-bearing tumor cells.

    abstract::Oncolytic herpes simplex virus (HSV) vectors have been used in early phase human clinical trials as a therapy for recurrent malignant glioblastoma. This treatment proved safe but limited improvements in patient survival were observed. The potency of these vectors might be enhanced by targeting vector infectivity to tu...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.22

    authors: Grandi P,Fernandez J,Szentirmai O,Carter R,Gianni D,Sena-Esteves M,Breakefield XO

    更新日期:2010-09-01 00:00:00

  • Mdr1 promoter-driven tumor necrosis factor-alpha expression for a chemotherapy-controllable combined in vivo gene therapy and chemotherapy of tumors.

    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

    authors: Walther W,Stein U,Fichtner I,Alexander M,Shoemaker RH,Schlag PM

    更新日期:2000-06-01 00:00:00

  • Suppression of the Ewing's sarcoma phenotype by FLI1/ERF repressor hybrids.

    abstract::Fusion of the 5' half of the Ewing's sarcoma (ES) gene EWS with the DNA-binding domain of several transcription factors has been detected in many human tumors. The t(11;22)(q24;q12) chromosomal translocation is specifically linked to ES and primitive neuroectodermal tumors and results, in the majority of cases, in the...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700220

    authors: Athanasiou M,LeGallic L,Watson DK,Blair DG,Mavrothalassitis G

    更新日期:2000-08-01 00:00:00

  • Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy.

    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

    authors: Jarnagin WR,Zager JS,Hezel M,Stanziale SF,Adusumilli PS,Gonen M,Ebright MI,Culliford A,Gusani NJ,Fong Y

    更新日期:2006-03-01 00:00:00

  • Development of a novel adenovirus-alphavirus hybrid vector with RNA replicon features for malignant hematopoietic cell transduction.

    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

    authors: Yang Y,Xiao F,Lu Z,Li Z,Zuo H,Zhang Q,Li Q,Wang H,Wang LS

    更新日期:2013-08-01 00:00:00

  • Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population.

    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

    authors: Yang HW,Lei P,Xie YC,Han ZL,Li D,Wang SH,Sun ZL

    更新日期:2017-06-01 00:00:00

  • Immunosuppression promotes reovirus therapy of colorectal liver metastases.

    abstract::Mortality due to colorectal cancer (CRC) is high and is associated with the development of liver metastases. Approximately 40% of human CRCs harbor an activating mutation in the KRAS oncogene. Tumor cells with activated KRAS are particularly sensitive to Reovirus T3D, a non-pathogenic oncolytic virus. The efficacy of ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700949

    authors: Smakman N,van der Bilt JD,van den Wollenberg DJ,Hoeben RC,Borel Rinkes IH,Kranenburg O

    更新日期:2006-08-01 00:00:00

  • Comparative assessment of TCRBV diversity in T lymphocytes present in blood, metastatic lesions, and DTH sites of two melanoma patients vaccinated with an IL-7 gene-modified autologous tumor cell vaccine.

    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

    authors: Carsana M,Tragni G,Nicolini G,Bersani I,Parmiani G,Anichini A,Sun YS,Möller P,Schadendorf D,Sensi ML

    更新日期:2002-03-01 00:00:00

  • Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI-p53 complexes.

    abstract::Lung metastases are a frequent complication of osteosarcoma and a treatment that would reduce the severity of this complication would be of great benefit to patients. We have used a formulation consisting of polyethyleneimine (PEI) and a p53 gene administered in aerosol to treat established lung micrometastases as a m...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700343

    authors: Densmore CL,Kleinerman ES,Gautam A,Jia SF,Xu B,Worth LL,Waldrep JC,Fung YK,T'Ang A,Knight V

    更新日期:2001-09-01 00:00:00

  • The chicken chorioallantoic membrane tumor assay as model for qualitative testing of oncolytic adenoviruses.

    abstract::Oncolytic adenoviruses are promising anticancer agents. To study and optimize their tumor-killing potency, genuine tumor models are required. Here we describe the use of the chicken chorioallantoic membrane (CAM) tumor model in studies on oncolytic adenoviral vectors. Suspensions of human melanoma, colorectal carcinom...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.68

    authors: Durupt F,Koppers-Lalic D,Balme B,Budel L,Terrier O,Lina B,Thomas L,Hoeben RC,Rosa-Calatrava M

    更新日期:2012-01-01 00:00:00

  • MicroRNA silencing improves the tumor specificity of adenoviral transgene expression.

    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

    authors: Card PB,Hogg RT,Gil Del Alcazar CR,Gerard RD

    更新日期:2012-07-01 00:00:00

  • Silencing of long non-coding RNA XIST represses gastric cancer progression through blocking NFκB pathway via inhibiting HNF4A-mediated transcription of EPHA1.

    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

    authors: Li P,Wang L,Li P,Hu F,Cao Y,Tang D,Ye G,Li H,Wang D

    更新日期:2020-11-16 00:00:00

  • Lipofection indirectly increases expression of endogenous major histocompatibility complex class I molecules on tumor cells.

    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:

    authors: Fox BA,Drury M,Hu HM,Cao Z,Huntzicker EG,Qie W,Urba WJ

    更新日期:1998-09-01 00:00:00

  • Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

    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

    authors: Dummer R,Bergh J,Karlsson Y,Horowitz JA,Mulder NH,Huinink DTB,Burg G,Hofbauer G,Osanto S

    更新日期:2000-07-01 00:00:00

  • Phase I trial of interferon-gamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma.

    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

    authors: Nemunaitis J,Fong T,Robbins JM,Edelman G,Edwards W,Paulson RS,Bruce J,Ognoskie N,Wynne D,Pike M,Kowal K,Merritt J,Ando D

    更新日期:1999-07-01 00:00:00

  • Eliciting protective immune responses against murine myeloma challenge in lymphopenia mice through adoptive transfer of tumor antigen-specific lymphocytes and immunization of tumor vaccine secreting mIL-21.

    abstract::Previous studies have indicated that the cytokine interleukin (IL)-21 may induce both innate and adaptive immune responses against tumors. The goal of this study was to evaluate a new adoptive immunotherapy strategy that combined lymphocytes from mice immunized with a murine myeloma vaccine secreting murine IL-21 (mIL...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.23

    authors: Dou J,Wu Y,Wang J,Zhao F,Chu L,Liu C,Wen P,Hu W,Hu K,He XF,Gu N

    更新日期:2010-10-01 00:00:00

  • Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus.

    abstract::Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700732

    authors: Lim HY,Ahn M,Chung HC,Gardner TA,Kao C,Lee SJ,Kim SJ

    更新日期:2004-08-01 00:00:00

  • Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells.

    abstract::Let-7 miRNAs are involved in carcinogenesis and tumor progression through their roles in maintaining differentiation and normal development. However, there is little research focusing on the effects of let-7 on Wnt-activated self-renewal of breast cancer stem cells. By analyzing the expression levels of let-7 family m...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2016.3

    authors: Sun X,Xu C,Tang SC,Wang J,Wang H,Wang P,Du N,Qin S,Li G,Xu S,Tao Z,Liu D,Ren H

    更新日期:2016-04-01 00:00:00

  • Apatinib prevents natural killer cell dysfunction to enhance the efficacy of anti-PD-1 immunotherapy in hepatocellular carcinoma.

    abstract::Apatinib, a selective vascular endothelial growth factor receptor 2-tyrosine kinase inhibitor, has demonstrated activity against a wide range of solid tumors, including advanced hepatocellular carcinoma (HCC). Preclinical and preliminary clinical results have confirmed the synergistic antitumor effects of apatinib in ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-020-0186-7

    authors: Yang Y,Wang C,Sun H,Jiang Z,Zhang Y,Pan Z

    更新日期:2020-06-12 00:00:00

  • Neuregulin receptor-mediated gene transfer by human epidermal growth factor receptor 2-targeted antibodies and neuregulin-1.

    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 co...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700069

    authors: Kern JA,Wakita R,Sliwkowski MX

    更新日期:1999-11-01 00:00:00

  • Locked nucleic acid inhibits miR-92a-3p in human colorectal cancer, induces apoptosis and inhibits cell proliferation.

    abstract::MicroRNAs (miRNAs) are a type of small noncoding RNAs that have a vital role in basic biological processes such as cellular growth, division and apoptosis. A change in the expression of miRNAs can induce many diseases. Recently, the role of miRNA in some of the cancers as a tumor suppressor and oncogene has been recog...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2016.10

    authors: Ahmadi S,Sharifi M,Salehi R

    更新日期:2016-07-01 00:00:00