Radiation increases the activity of oncolytic adenovirus cancer gene therapy vectors that overexpress the ADP (E3-11.6K) protein.

Abstract:

:We have described three potential adenovirus type 5 (Ad5)-based replication-competent cancer gene therapy vectors named KD1, KD3, and VRX-007. All three vectors overexpress an Ad5 protein named Adenovirus Death Protein (ADP, also named E3-11.6 K protein). ADP is required for efficient lysis of Ad5-infected cells and spread of virus from cell to cell, and thus its overexpression increases the oncolytic activity of the vectors. KD1 and KD3 contain mutations in the Ad5 E1A gene that knock out binding of the E1A proteins to cellular p300/CBP and pRB; these mutations allow KD1 and KD3 to grow well in cancer cells but not in normal cells. VRX-007 has wild-type E1A. Here we report that radiation increases the oncolytic activity of KD1, KD3, and VRX-007. This increased activity was observed in cultured cells, and it was not because of radiation-induced replication of the vectors. The combination of radiation plus KD3 suppressed the growth of A549 lung adenocarcinoma xenografts in nude mice more efficiently than radiation alone or KD3 alone. The combination of ADP-overexpressing vectors and radiation may have potential in treating cancer.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Toth K,Tarakanova V,Doronin K,Ward P,Kuppuswamy M,Locke JE,Dawson JE,Kim HJ,Wold WS

doi

10.1038/sj.cgt.7700555

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

193-200

issue

3

eissn

0929-1903

issn

1476-5500

pii

7700555

journal_volume

10

pub_type

杂志文章
  • 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

  • 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

  • Molecular conjugate vectors mediate efficient gene transfer into gastrointestinal epithelial cells.

    abstract::Transfer of genes to the gastrointestinal epithelium would be advantageous from investigational and therapeutic standpoints. Efficient transfer of DNA to the intestinal epithelial cells, however, has been problematic with conventional viral and nonviral vectors. As an alternative, we have utilized molecular conjugate ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Batra RK,Berschneider H,Curiel DT

    更新日期:1994-09-01 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

  • Arming oncolytic reovirus with GM-CSF gene to enhance immunity.

    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

    authors: Kemp V,van den Wollenberg DJM,Camps MGM,van Hall T,Kinderman P,Pronk-van Montfoort N,Hoeben RC

    更新日期:2019-09-01 00:00:00

  • A novel fusion suicide gene yeast CDglyTK plays a role in radio-gene therapy of nasopharyngeal carcinoma.

    abstract::To investigate a novel suicide gene for nasopharyngeal carcinoma (NPC) therapy, the yCDglyTK gene was constructed by fusing yeast cytosine deaminase (CD) and herpes simplex type 1 thymidine kinase. The expression of the yCDglyTK gene was detected by RT-PCR and Western blotting, and its bioactivity was demonstrated by ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700728

    authors: Xia K,Liang D,Tang A,Feng Y,Zhang J,Pan Q,Long Z,Dai H,Cai F,Wu L,Zhao S,Chen Z,Xia J

    更新日期:2004-12-01 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

  • 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

  • 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

  • Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C)-stimulated macrophages.

    abstract::Macrophages plasticity is a key feature in cancer progression. Neoplastic cells can alter their immune functions and orient them into a pro-tumoral phenotype. In this context, we developed a new therapeutic strategy to switch macrophages phenotype and reactivate their anti-tumoral functions. We showed a dual activity ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-020-00286-1

    authors: Rose M,Duhamel M,Aboulouard S,Kobeissy F,Tierny D,Fournier I,Rodet F,Salzet M

    更新日期:2021-01-05 00:00:00

  • Antitumor effects of non-replicative herpes simplex vectors expressing antiangiogenic proteins and thymidine kinase on Lewis lung carcinoma establishment and growth.

    abstract::There is growing evidence that combinations of antiangiogenic proteins with other antineoplastic treatments such as chemo- or radiotherapy and suicide genes-mediated tumor cytotoxicity lead to synergistic effects. In the present work, we tested the activity of two non-replicative herpes simplex virus (HSV)-1-based vec...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7701058

    authors: Berto E,Bozac A,Volpi I,Lanzoni I,Vasquez F,Melara N,Manservigi R,Marconi P

    更新日期:2007-09-01 00:00:00

  • Enhancement of adenoviral transduction with polycationic liposomes in vivo.

    abstract::Although the high transfection efficiency with adenovirus in vitro is well documented, it is still not clear whether adenoviral vectors are effective in vivo in solid tumor models. In our preliminary experiment, transduction of tumor tissue was limited to just around the injection site after intratumoral injection of ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700237

    authors: Lee SG,Yoon SJ,Kim CD,Kim K,Lim DS,Yeom YI,Sung MW,Heo DS,Kim NK

    更新日期:2000-10-01 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

    doi:10.1038/sj.cgt.7700538

    authors: Mastrangelo MJ,Lattime EC

    更新日期:2002-12-01 00:00:00

  • Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma.

    abstract::Nuclear factor-kappa B (NF-κB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-κB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-κB has been developed. To determin...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.75

    authors: Nishimura A,Akeda K,Matsubara T,Kusuzaki K,Matsumine A,Masuda K,Gemba T,Uchida A,Sudo A

    更新日期:2011-04-01 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

  • 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

    doi:10.1038/s41417-020-00216-1

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

    更新日期:2020-12-09 00:00:00

  • Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

    abstract::As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.cgt.7700965

    authors: Norris JS,Bielawska A,Day T,El-Zawahri A,ElOjeimy S,Hannun Y,Holman D,Hyer M,Landon C,Lowe S,Dong JY,McKillop J,Norris K,Obeid L,Rubinchik S,Tavassoli M,Tomlinson S,Voelkel-Johnson C,Liu X

    更新日期:2006-12-01 00:00:00

  • The carcinoma-specific epithelial glycoprotein-2 promoter controls efficient and selective gene expression in an adenoviral context.

    abstract::Adenoviral vectors are widely used in cancer gene therapy. After systemic administration however, the majority of the virus homes to the liver and the expressed transgene may cause hepatotoxicity. To restrict transgene expression to tumor cells, tumor- or tissue-specific promoters are utilized. The tumor antigen epith...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700882

    authors: Gommans WM,van Eert SJ,McLaughlin PM,Harmsen MC,Yamamoto M,Curiel DT,Haisma HJ,Rots MG

    更新日期:2006-02-01 00:00:00

  • Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N.

    abstract::Drug metabolizing transgene products, which activate bioreductive cytotoxins, can be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6 transgenes ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700933

    authors: Yakkundi A,McErlane V,Murray M,McCarthy HO,Ward C,Hughes CM,Patterson LH,Hirst DG,McKeown SR,Robson T

    更新日期:2006-06-01 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

  • A novel gene transfer strategy that combines promoter and transgene activities for improved tumor cell inhibition.

    abstract::Typically, gene transfer strategies utilize a promoter/transgene arrangement that treat these elements independently and do not offer any interplay between them. Our goal was to establish a promoter/transgene combination that would result in improvement in both expression and therapeutic effect by utilizing the transc...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700846

    authors: Strauss BE,Bajgelman MC,Costanzi-Strauss E

    更新日期:2005-12-01 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

  • Transcellular transfer of active HSV-1 thymidine kinase mediated by an 11-amino-acid peptide from HIV-1 Tat.

    abstract::Suicide gene therapy using herpes simplex virus type-1 (HSV-1) thymidine kinase (TK) is a widely exploited approach for gene therapy of cancer and other hyperproliferative disorders. Despite its popularity, clinical success has been so far hampered mostly by the relative inefficiency of TK gene transfer and its limite...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700526

    authors: Tasciotti E,Zoppè M,Giacca M

    更新日期:2003-01-01 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

  • Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral vector inhibits IL-6-dependent proliferation of multiple myeloma cells.

    abstract::Multiple myeloma (MM) accounts for 10% of hematological malignant disorders. Its refractory nature indicates the necessity of developing novel therapeutic modalities. Since interleukin 6 (IL-6) is one of the major growth factors for MM cells, we expressed suppressor of cytokine signaling-1 (SOCS-1), one of the blockad...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700873

    authors: Yamamoto M,Nishimoto N,Davydova J,Kishimoto T,Curiel DT

    更新日期:2006-02-01 00:00:00

  • Gene therapy of metastatic colon carcinoma: regression of multiple hepatic metastases by adenoviral expression of bacterial cytosine deaminase.

    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

    authors: Block A,Freund CT,Chen SH,Nguyen KP,Finegold M,Windler E,Woo SL

    更新日期:2000-03-01 00:00:00

  • Infiltration of dendritic cells and T lymphocytes predicts favorable outcome in epithelial ovarian cancer.

    abstract::We aimed to analyze the association between the distribution of dendritic cells (DC) with expression of tumor-infiltrating T lymphocytes and clinicopathologic parameters with prognosis in epithelial ovarian cancer (EOC). Thirty-three EOC patient samples were surgically resected, and pathology was examined for clinicop...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2015.7

    authors: Zhang Z,Huang J,Zhang C,Yang H,Qiu H,Li J,Liu Y,Qin L,Wang L,Hao S,Zhang F,Wang X,Shan B

    更新日期:2015-03-01 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 the prodrug-activating enzyme DT-diaphorase via Ad5 delivery to human colon carcinoma cells in vitro.

    abstract::Intratumoral injection of recombinant adenoviral type 5 (Ad5) vectors that carry prodrug-activating enzymes like DT-diaphorase (DTD) could be used to selectively target tumor cells for chemotherapy. To demonstrate the feasibility of this approach, Ad5 vectors were constructed, which express human DTD minigenes for bot...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700430

    authors: Misra V,Klamut HJ,Rauth AM

    更新日期:2002-02-01 00:00:00

  • Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy.

    abstract::The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatm...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700331

    authors: Rodolfo M,Catò EM,Soldati S,Ceruti R,Asioli M,Scanziani E,Vezzoni P,Parmiani G,Sacco MG

    更新日期:2001-07-01 00:00:00