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
  • 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

  • Gene therapy for castration-resistant prostate cancer cells using JC polyomavirus-like particles packaged with a PSA promoter driven-suicide gene.

    abstract::Prostate cancer is the second most common cancer in men globally. Prostate cancer patients at advanced stages are usually treated with androgen deprivation therapy (ADT). However, with disease progression, it often becomes the incurable castration-resistant prostate cancer (CRPC). JC polyomavirus (JCPyV) is a human DN...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-019-0083-0

    authors: Lin MC,Wang M,Chou MC,Chao CN,Fang CY,Chen PL,Chang D,Shen CH

    更新日期:2019-07-01 00:00:00

  • Mesenchymal stem cell: a new horizon in cancer gene therapy.

    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

    authors: Mohammadi M,Jaafari MR,Mirzaei HR,Mirzaei H

    更新日期:2016-09-01 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

    doi:

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

    更新日期:1996-11-01 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

    doi:10.1038/sj.cgt.7700475

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

    更新日期:2002-07-01 00:00:00

  • Targeting gene expression to tumor cells with loss of wild-type p53 function.

    abstract::The tumor suppressor protein p53 is a transcription factor that can positively regulate the expression of critical target genes involved in negative control of cell growth or induction of apoptosis; p53 is also able to suppress the transcription of other genes by virtue of its ability to bind components of the basal t...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700091

    authors: Zhu J,Gao B,Zhao J,Balmain A

    更新日期:2000-01-01 00:00:00

  • Intrabody targeting vascular endothelial growth factor receptor-2 mediates downregulation of surface localization.

    abstract::Angiogenesis is among the most important mechanisms that helps cancer cells to survive, grow and undergo metastasis. Therefore, inhibiting angiogenesis will suppress tumor growth. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are believed to be important players of angiogenesis. The goal of this s...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2016.76

    authors: Alirahimi E,Ashkiyan A,Kazemi-Lomedasht F,Azadmanesh K,Hosseininejad-Chafi M,Habibi-Anbouhi M,Moazami R,Behdani M

    更新日期:2017-01-01 00:00:00

  • An HSVtk-mediated local and distant antitumor bystander effect in tumors of head and neck origin in athymic mice.

    abstract::The "bystander effect," produced by ganciclovir-mediated killing of cells transduced with a herpes simplex virus thymidine kinase (HSVtk) gene, defines the cooperative killing of non-HSVtk-transduced cells. In vitro, a major contributor to this phenomenon is metabolic cooperation involving transfer of cytotoxic small ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Bi W,Kim YG,Feliciano ES,Pavelic L,Wilson KM,Pavelic ZP,Stambrook PJ

    更新日期:1997-07-01 00:00:00

  • MicroRNA21 and the various types of myeloid leukemia.

    abstract::Myeloid leukemia (ML) is heterogeneous cancer classified by abnormal growth of myeloid cells due to genetic aberrations and mutations. It is generally categorized by clonal disorders of hematopoietic stem cells and differentiation. The molecular mechanism behind the myeloid malignancies is not yet known, but recent se...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/s41417-018-0025-2

    authors: Panagal M,S R SK,P S,M B,M K,Gopinathe V,Sivakumare P,Sekar D

    更新日期:2018-08-01 00:00:00

  • Effectiveness of cancer vaccine therapy using cells transduced with the interleukin-12 gene combined with systemic interleukin-18 administration.

    abstract::We introduced the interleukin-12 (IL-12) gene into mouse renal cell carcinoma (RenCa) cells to develop a tumor vaccine and to examine mechanisms of tumor rejection. IL-12-secreting RenCa (RenCa/IL-12) cells were completely rejected when implanted into syngeneic BALB/c but not athymic nude mice, suggesting that T cells...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700083

    authors: Hara I,Nagai H,Miyake H,Yamanaka K,Hara S,Micallef MJ,Kurimoto M,Gohji K,Arakawa S,Ichihashi M,Kamidono S

    更新日期:2000-01-01 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

    doi:10.1038/s41417-018-0012-7

    authors: Gacerez AT,Sentman CL

    更新日期:2018-06-01 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

    doi:10.1038/s41417-019-0082-1

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

    更新日期:2019-07-01 00:00:00

  • Role of temperature-independent lipoplex-cell membrane interactions in the efficiency boost of multicomponent lipoplexes.

    abstract::Multicomponent lipoplexes have recently emerged as especially promising transfection candidates, as they are from 10 to 100 times more efficient than binary complexes usually employed for gene delivery purposes. Previously, we investigated a number of chemical-physical properties of DNA-lipid complexes that were propo...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.12

    authors: Marchini C,Pozzi D,Montani M,Alfonsi C,Amici A,Candeloro De Sanctis S,Digman MA,Sanchez S,Gratton E,Amenitsch H,Fabbretti A,Gualerzi CO,Caracciolo G

    更新日期:2011-08-01 00:00:00

  • Correction to: Schwannoma gene therapy by adeno-associated virus delivery of the pore-forming protein Gasdermin-D.

    abstract::The original version of this Article contained an error in the spelling of the author Ahmed Abdelanabi, which was incorrectly given as Abdelanabi Ahmed. This has now been corrected in both the PDF and HTML versions of the Article. ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41417-019-0096-8

    authors: Ahmed SG,Abdelanabi A,Doha M,Brenner GJ

    更新日期:2020-04-01 00:00:00

  • Generation of an adenoviral vector containing an addition of a heterologous ligand to the serotype 3 fiber knob.

    abstract::As an initial assessment of the feasibility of employing the adenovirus serotype 3 (Ad3) fiber knob as a locale for introducing a tropism-modifying motif, we generated an adenoviral vector containing a six-histidine tag genetically fused to the carboxy-terminus of the Ad3 fiber knob. The heterologous tag proved to be ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700543

    authors: Uil TG,Seki T,Dmitriev I,Kashentseva E,Douglas JT,Rots MG,Middeldorp JM,Curiel DT

    更新日期:2003-02-01 00:00:00

  • Calcium-sensing receptor antagonist NPS-2143 suppresses proliferation and invasion of gastric cancer cells.

    abstract::NPS-2143 is a calcium-sensing receptor (CaSR) antagonist that has been demonstrated to possess anticancer activity. To date, the effects of NPS-2143 on gastric cancer (GC) cell growth, motility, and apoptosis have not been investigated. In the present study, we firstly investigated the expression of CaSR in GC tissues...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-019-0128-4

    authors: Zhang ZL,Li ZR,Li JS,Wang SR

    更新日期:2020-08-01 00:00:00

  • Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference.

    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

    authors: Rao DD,Maples PB,Senzer N,Kumar P,Wang Z,Pappen BO,Yu Y,Haddock C,Jay C,Phadke AP,Chen S,Kuhn J,Dylewski D,Scott S,Monsma D,Webb C,Tong A,Shanahan D,Nemunaitis J

    更新日期:2010-11-01 00:00:00

  • Screening siRNAs targeting a novel gene (HA117) and the development of a derivative recombinant adenovirus delivery system.

    abstract::A novel gene, HA117, was discovered in our previous work. Using the pSOS-HUS vector method which we designed at previous study, we screened for small interfering RNAs (siRNAs) that targeted HA117. The pSOS-HUS siRNA screening results were verified and a delivery system was developed that contained a recombinant adenov...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.32

    authors: Zheng GH,Luo Q,Jin XQ,Guo YX,Xu YH

    更新日期:2011-09-01 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

  • Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors.

    abstract::Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2008.31

    authors: Yaacov B,Eliahoo E,Lazar I,Ben-Shlomo M,Greenbaum I,Panet A,Zakay-Rones Z

    更新日期:2008-12-01 00:00:00

  • Dendritic cells engineered to secrete anti-GITR antibodies are effective adjuvants to dendritic cell-based immunotherapy.

    abstract::A number of monoclonal antibodies (mAbs) have been studied for their ability to enhance immune responses. Although these antibodies are effective in pre-clinical and clinical studies, they are costly and have occasionally been associated with adverse effects such as autoimmunity and cytokine storm. Numerous studies ha...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2009.39

    authors: Boczkowski D,Lee J,Pruitt S,Nair S

    更新日期:2009-12-01 00:00:00

  • Immunogene approach toward cancer therapy using erythrocyte growth factor receptor-mediated gene delivery.

    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:

    authors: Shimizu N,Chen J,Gamou S,Takayanagi A

    更新日期:1996-03-01 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

    doi:

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

    更新日期:1997-01-01 00:00:00

  • Correction: Specific driving of the suicide E gene by the CEA promoter enhances the effects of paclitaxel in lung cancer.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Cancer gene therapy

    pub_type: 已发布勘误

    doi:10.1038/s41417-020-0166-y

    authors: Ballesteros ARR,Hernández R,Perazzoli G,Cabeza L,Melguizo C,Vélez C,Prados J

    更新日期:2020-06-01 00:00:00

  • Canarypox virus expressing wild type p53 for gene therapy in murine tumors mutated in p53.

    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

    authors: Odin L,Favrot M,Poujol D,Michot JP,Moingeon P,Tartaglia J,Puisieux I

    更新日期:2001-02-01 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

  • Recombinant vaccinia expressing interleukin-2 for cancer gene therapy.

    abstract::Use of a recombinant vaccinia virus expressing human interleukin-2 (IL-2) was evaluated for preparation of tumor vaccines. A/J mice were immunized against neuroblastoma (C1300) cells using a preparation of C1300 cells infected/transfected with the recombinant virus, vCF13, expressing IL-2. A second recombinant vaccini...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Qin H,Chatterjee SK

    更新日期:1996-05-01 00:00:00

  • Endostatin gene therapy delivered by attenuated Salmonella typhimurium in murine tumor models.

    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

    authors: Liang K,Liu Q,Li P,Han Y,Bian X,Tang Y,Kong Q

    更新日期:2018-08-01 00:00:00

  • Does preventive vaccination with engineered tumor cells work in cancer-prone transgenic mice?

    abstract::The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Morel A,de La Coste A,Fernandez N,Berson A,Kaybanda M,Molina T,Briand P,Haddada H,Guillet JG,Antoine B,Viguier M,Kahn A

    更新日期:1998-03-01 00:00:00

  • Triplex-forming oligodeoxynucleotides targeting survivin inhibit proliferation and induce apoptosis of human lung carcinoma cells.

    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

    authors: Shen C,Buck A,Polat B,Schmid-Kotsas A,Matuschek C,Gross HJ,Bachem M,Reske SN

    更新日期:2003-05-01 00:00:00