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


: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.


Cancer Gene Ther


Cancer gene therapy


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




Has Abstract


2006-10-01 00:00:00














  • Use of targeted cationic liposomes in enhanced DNA delivery to cancer cells.

    abstract::Cationic liposomes are considered to be safe vectors for gene transfer, but they are less efficient at delivering DNA to cells when compared with retroviral vectors. Cationic liposomes complexed with DNA were targeted to specific cells in vitro by means of monoclonal antibodies (mAbs) or ligands associated with the li...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Kao GY,Change LJ,Allen TM

    更新日期:1996-07-01 00:00:00

  • Oral contrast enhances the resolution of in-life NIS reporter gene imaging.

    abstract::Sodium iodide symporter (NIS) reporter gene imaging is an excellent technology for noninvasive cell fate determination in living animals unless the NIS-transduced cells reside in perigastric organs such as the spleen, liver, diaphragm, omentum, pancreas, perigastric lymph nodes or perigastric tumor deposits. Here we r...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Suksanpaisan L,Pham L,McIvor S,Russell SJ,Peng KW

    更新日期:2013-11-01 00:00:00

  • Cellular and humoral immune responses to adenovirus and p53 protein antigens in patients following intratumoral injection of an adenovirus vector expressing wild-type. P53 (Ad-p53).

    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


    authors: Yen N,Ioannides CG,Xu K,Swisher SG,Lawrence DD,Kemp BL,El-Naggar AK,Cristiano RJ,Fang B,Glisson BS,Hong WK,Khuri FR,Kurie JM,Lee JJ,Lee JS,Merritt JA,Mukhopadhyay T,Nesbitt JC,Nguyen D,Perez-Soler R,Pisters KM,P

    更新日期:2000-04-01 00:00:00

  • Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects.

    abstract::We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected int...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Ugai S,Shimozato O,Yu L,Wang YQ,Kawamura K,Yamamoto H,Yamaguchi T,Saisho H,Sakiyama S,Tagawa M

    更新日期:2003-10-01 00:00:00

  • Lipid-coated polyplexes for targeted gene delivery to ovarian carcinoma cells.

    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


    authors: Mastrobattista E,Kapel RH,Eggenhuisen MH,Roholl PJ,Crommelin DJ,Hennink WE,Storm G

    更新日期:2001-06-01 00:00:00

  • Targeting MMP-9, uPAR, and cathepsin B inhibits invasion, migration and activates apoptosis in prostate cancer cells.

    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


    authors: Nalla AK,Gorantla B,Gondi CS,Lakka SS,Rao JS

    更新日期:2010-09-01 00:00:00

  • Combined suicide and granulocyte-macrophage colony-stimulating factor gene therapy induces complete tumor regression and generates antitumor immunity.

    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


    authors: Jones RK,Pope IM,Kinsella AR,Watson AJ,Christmas SE

    更新日期:2000-12-01 00:00:00

  • Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor rnasin.

    abstract::The growth of new blood vessels is an essential condition for the development of tumors with a diameter greater than 1-2 mm and also for their metastatic dissemination. RNasin, the placental ribonuclease inhibitor, is known to have antiangiogenic activity through the inhibition of angiogenin and basic fibroblast growt...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Botella-Estrada R,Malet G,Revert F,Dasí F,Crespo A,Sanmartín O,Guillén C,Aliño SF

    更新日期:2001-04-01 00:00:00

  • Immunotherapy for murine K1735 melanoma: combinatorial use of recombinant adenovirus expressing CD40L and other immunomodulators.

    abstract::We have constructed and tested five recombinant adenoviruses (Ads) that express a variety of immunomodulators, including CD40 ligand (CD40L), a potent costimulator of several components of the immune system. We demonstrate that CD40L expressed from Ad in K1735 mouse melanoma cells leads to a strong reduction in tumori...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Peter I,Nawrath M,Kamarashev J,Odermatt B,Mezzacasa A,Hemmi S

    更新日期:2002-07-01 00:00:00

  • microRNA-let-7e in serum-derived exosomes inhibits the metastasis of non-small-cell lung cancer in a SUV39H2/LSD1/CDH1-dependent manner.

    abstract::Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of seru...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Xu S,Zheng L,Kang L,Xu H,Gao L

    更新日期:2020-12-09 00:00:00

  • Virotherapy clinical trials for regional disease: in situ immune modulation using recombinant poxvirus vectors.

    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


    authors: Mastrangelo MJ,Lattime EC

    更新日期:2002-12-01 00:00:00

  • Immunotherapy targeting HER2 with genetically modified T cells eliminates tumor-initiating cells in osteosarcoma.

    abstract::Despite radical surgery and multi-agent chemotherapy, less than one third of patients with recurrent or metastatic osteosarcoma (OS) survive. The limited efficacy of current therapeutic approaches to target tumor-initiating cells (TICs) may explain this dismal outcome. The purpose of this study was to assess the impac...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Rainusso N,Brawley VS,Ghazi A,Hicks MJ,Gottschalk S,Rosen JM,Ahmed N

    更新日期:2012-03-01 00:00:00

  • Recipient C6 rs9200 genotype is associated with hepatocellular carcinoma recurrence after orthotopic liver transplantation in a Han Chinese population.

    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


    authors: Wang Z,Liao J,Wu S,Li C,Fan J,Peng Z

    更新日期:2016-06-01 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


    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

  • Expression of costimulatory molecules: B7 and ICAM up-regulation after treatment with a suicide gene.

    abstract::The herpes simplex virus thymidine kinase gene (HSV-TK) in combination with ganciclovir (GCV), is currently being used in gene therapy-based clinical trials for cancer treatment. Its therapeutic effect is based on a "bystander effect" whereby HSV-TK gene-modified tumor cells are toxic to nearby unmodified tumor cells ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Ramesh R,Munshi A,Abboud CN,Marrogi AJ,Freeman SM

    更新日期:1996-11-01 00:00:00

  • Downregulation of microRNA-145 promotes epithelial-mesenchymal transition via regulating Snail in osteosarcoma.

    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


    authors: Zhang Z,Zhang M,Chen Q,Zhang Q

    更新日期:2017-02-01 00:00:00

  • Inhibitory effects of interferon-gamma plasmid DNA on DMBA-TPA induced mouse skin carcinogenesis.

    abstract::Interferon-gamma (IFN-γ) exhibits biological activities that are considered to have important roles in tumor suppression. Therefore, the IFN-γ gene is a potential candidate for in vivo cytokine gene therapy against skin cancer. The present study evaluated the efficacy of a hydrodynamics-based IFN-γ gene transfection f...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Ko JH,Jung BG,Park YS,Lee BJ

    更新日期:2011-09-01 00:00:00

  • Identification of differentially expressed genes and their upstream regulators in colorectal cancer.

    abstract::To identify the differentially expressed genes (DEGs) and their transcription factors (TFs) in colorectal cancer (CRC). We performed an integrated analysis of microarray studies. Functional annotation and CRC-specific transcriptional regulatory network construction were performed. Expression of selected DEGs and TFs w...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Liu HY,Zhang CJ

    更新日期:2017-06-01 00:00:00

  • Immune properties of recombinant vaccinia virus encoding CD154 (CD40L) are determined by expression of virally encoded CD40L and the presence of CD40L protein in viral particles.

    abstract::Expression of costimulatory molecules by recombinant poxviruses is a promising strategy for enhancing therapeutic vaccines. CD40-CD40L interactions are critical for conditioning dendritic cells (DC) and priming T- and B-cell immunity. We constructed a vaccinia virus expressing murine CD40L (rV-CD40L) and studied its i...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Bereta M,Bereta J,Park J,Medina F,Kwak H,Kaufman HL

    更新日期:2004-12-01 00:00:00

  • Expression of an antisense transforming growth factor-beta1 transgene reduces tumorigenicity of EMT6 mammary tumor cells.

    abstract::Transforming growth factor-beta (TGF-beta) is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-beta by malignant cells may therefore be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In order to evaluate the role of tumor-derived TGF-beta on tumor...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Park JA,Wang E,Kurt RA,Schluter SF,Hersh EM,Akporiaye ET

    更新日期:1997-01-01 00:00:00

  • Cotargeting tumor and tumor endothelium effectively inhibits the growth of human prostate cancer in adenovirus-mediated antiangiogenesis and oncolysis combination therapy.

    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


    authors: Jin F,Xie Z,Kuo CJ,Chung LW,Hsieh CL

    更新日期:2005-03-01 00:00:00

  • Recombinant vesicular stomatitis virus targeted to Her2/neu combined with anti-CTLA4 antibody eliminates implanted mammary tumors.

    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


    authors: Gao Y,Whitaker-Dowling P,Griffin JA,Barmada MA,Bergman I

    更新日期:2009-01-01 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


    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

  • 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


    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

  • 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


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

    更新日期:2020-06-12 00:00:00

  • Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo.

    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


    authors: Schirrmann T,Pecher G

    更新日期:2002-04-01 00:00:00

  • T-bet promotes potent antitumor activity of CD4+ CAR T cells.

    abstract::Chimeric antigen receptor (CAR) therapy has shown promise against B cell malignancies in the clinic. However, limited success in patients with solid tumors has prompted the development of new CAR strategies. In this study, a B7H6-specific CAR was combined with different variants of T-bet, a transcription factor that a...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Gacerez AT,Sentman CL

    更新日期:2018-06-01 00:00:00

  • Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.

    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


    authors: Jang S,Yu XM,Odorico S,Clark M,Jaskula-Sztul R,Schienebeck CM,Kupcho KR,Harrison AD,Winston-McPherson GN,Tang W,Chen H

    更新日期:2015-08-01 00:00:00

  • Author Correction: BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction.

    abstract::All animal experiments were approved by the Animal Care and Use Committee (ACUC), Louisiana State University Health Science Center and not The People's Hospital of Liaoning Province as indicated in the original version of the Article. The PDF and HTML versions of the Article have been modified accordingly. ...

    journal_title:Cancer gene therapy

    pub_type: 已发布勘误


    authors: Yao Z,Yang S,Zhao H,Yang H,Jiang X

    更新日期:2019-07-01 00:00:00

  • Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor.

    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


    authors: Peng DJ,Sun J,Wang YZ,Tian J,Zhang YH,Noteborn MH,Qu S

    更新日期:2007-01-01 00:00:00