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 tumor cells. Glioma tumors often express a mutant form (vIII) of the epidermal growth factor receptor (EGFR) resulting in the presence of a novel epitope on the cell surface. This epitope is specifically recognized by a single-chain antibody designated MR1-1. HSV-1 infection involves initial binding to heparan sulfate (HS) on the cell surface mediated primarily by the viral envelope, glycoprotein C (gC). Here we joined the MR1-1 single-chain antibody (scFv) to the gC sequence deleted for the HS-binding domain as a means of targeting viral attachment to EGFRvIII on glial tumor cells. Virions bearing MR1-1-modified gC had fivefold increased infectivity for EGFRvIII-bearing human glioma U87 cells compared to mutant receptor-deficient cells. Further, MR1-1/EGFRvIII-mediated infection was more efficient for EGFRvIII-positive cells than was wild-type virus for either positive or negative cells. Sustained infection of EGFRvIII+ glioma cells by MR1-1-modified gC-bearing oncolytic virus, as compared to wild-type gC oncolytic virus, was also shown in subcutaneous tumors in vivo using firefly luciferase as a reporter of infection. These data show that HSV tropism can be manipulated so that virions recognize a cell-specific binding site with increased infectivity for the target cell. The retargeting of HSV infection to tumor cells should enhance vector specificity, tumor cell killing and vector safety.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

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

doi

10.1038/cgt.2010.22

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

655-63

issue

9

eissn

0929-1903

issn

1476-5500

pii

cgt201022

journal_volume

17

pub_type

杂志文章
  • Adenovirus-mediated overexpression of Fas induces apoptosis of gliomas.

    abstract::Gliomas express a higher amount of Fas than normal brain tissue. It is of interest to know whether expression of the Fas receptor is unfavorable to the antiapoptotic pathways in gliomas. In this study, we introduced the Fas gene via an adenovirus vector (Adeno-Fas) into the A-172, U251, and U-373 MG glioma cell lines,...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700110

    authors: Shinoura N,Ohashi M,Yoshida Y,Kirino T,Asai A,Hashimoto M,Hamada H

    更新日期:2000-02-01 00:00:00

  • microRNA-9-5p regulates the mitochondrial function of hepatocellular carcinoma cells through suppressing PDK4.

    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

    authors: Si T,Ning X,Zhao H,Zhang M,Huang P,Hu Z,Yang L,Lin L

    更新日期:2020-11-30 00:00:00

  • Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3.

    abstract::Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It is still unclear if and how miRNAs-221/222 are implicated in breast cancer and the resistance to estrogen receptor modulator tamoxifen. We investigated the roles and mechanisms of miR-221/222 in breast cancer cells, particularly in modula...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2014.29

    authors: Gan R,Yang Y,Yang X,Zhao L,Lu J,Meng QH

    更新日期:2014-07-01 00:00:00

  • Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma.

    abstract::Clear cell renal cell carcinoma (ccRCC) is the highest mortality, invasion, and metastasis subtype of renal cell carcinoma. Bone morphogenetic protein (BMP) family has recently emerged as a group of cancer-related proteins in multiple pathogenesis of cancers. Currently, little is known about the prediction role of BMP...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-019-0107-9

    authors: Xiao W,Wang X,Wang T,Xing J

    更新日期:2020-05-01 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

    doi:10.1038/sj.cgt.7700259

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

    更新日期:2000-12-01 00:00:00

  • Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand.

    abstract::The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the i...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-020-00239-8

    authors: Yu J,Yang K,Zheng J,Zhao W,Sun X

    更新日期:2020-10-13 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

  • 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

    doi:10.1038/sj.cgt.7700985

    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

  • 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

  • Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo.

    abstract::Gene therapy for prostate cancer may be realized through transduction of whole genes, such as PSA or PSMA, into immunotherapeutic dendritic cells (DCs). An oncoretroviral vector encoding human PSMA and a bicistronic oncoretroviral vector encoding human PSA and cell surface CD25 cDNAs were constructed. Remarkably, tran...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700810

    authors: Medin JA,Liang SB,Hou JW,Kelley LS,Peace DJ,Fowler DH

    更新日期:2005-06-01 00:00:00

  • TMB: a promising immune-response biomarker, and potential spearhead in advancing targeted therapy trials.

    abstract::Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/s41417-020-0174-y

    authors: Choucair K,Morand S,Stanbery L,Edelman G,Dworkin L,Nemunaitis J

    更新日期:2020-12-01 00:00:00

  • Papillomaviruses as targets for cancer gene therapy.

    abstract::The human papillomaviruses (HPVs) are a diverse group of infectious agents, some of which are a causative agent of human cancers. Cervical cancer and oral cancer are closely associated with specific types of HPV, and the tumors grow only if there is continual expression of the viral E6 and E7 genes. Evidence from in v...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.cgt.7700926

    authors: Shillitoe EJ

    更新日期:2006-05-01 00:00:00

  • Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses.

    abstract::Oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a variety of cancers. We recently developed MOA5, a tumor-specific midkine promoter-regulated oncolytic vector based on human adenovirus serotype 5 (Ad5). We modified the binding tropism of MOA5 by replacing the cell-binding domain of the ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2014.7

    authors: Takagi-Kimura M,Yamano T,Tagawa M,Kubo S

    更新日期:2014-03-01 00:00:00

  • Use of the EGP-2/Ep-CAM promoter for targeted expression of heterologous genes in carcinoma derived cell lines.

    abstract::EGP-2, also known as Ep-CAM, is expressed at high levels on the surface of most carcinomas and is therefore considered an attractive target for anticancer strategies. To explore the mechanisms regulating the expression of EGP-2, sequences 3.4 kb upstream of the transcription start site were isolated and assayed for th...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700725

    authors: McLaughlin PM,Trzpis M,Kroesen BJ,Helfrich W,Terpstra P,Dokter WH,Ruiters MH,de Leij LF,Harmsen MC

    更新日期:2004-09-01 00:00:00

  • Induction of systemic antitumor immunity by gene transfer of mammalian heat shock protein 70.1 into tumors in situ.

    abstract::Heat shock proteins (hsps) chaperone cytosolic peptides, forming complexes that stimulate antitumor immunity. Hsps facilitate signal 1 in the two-signal model of T-cell costimulation, whereas cell adhesion molecules such as B7.1 provide secondary (signal 2) costimulatory signals. B7.1 gene transfer into tumors in situ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700395

    authors: Rafiee M,Kanwar JR,Berg RW,Lehnert K,Lisowska K,Krissansen GW

    更新日期:2001-12-01 00:00:00

  • Virotherapy induces massive infiltration of neutrophils in a subset of tumors defined by a strong endogenous interferon response activity.

    abstract::Oncolytic virotherapy has shown substantial promises as an alternative therapeutic modality for solid tumors in both preclinical studies and clinical trials. The main therapeutic activity of virotherapy derives from the direct lytic effect associated with virus replication and the induction of host immune responses to...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.46

    authors: Fu X,Tao L,Rivera A,Xu H,Zhang X

    更新日期:2011-11-01 00:00:00

  • Redirected cellular cytotoxicity by infection of effector cells with a recombinant vaccinia virus encoding a tumor-specific monoclonal antibody.

    abstract::Cytotoxicity is an important function of the immune system that results in the destruction of cellular targets by humoral and/or cellular mechanisms. We wanted to assess the possibility of targeting the lytic function of immune cells toward cancer cells, which express the gene coding for a known tumor antigen (Ag) (GA...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700161

    authors: Paul S,Bizouarne N,Dott K,Ruet L,Dufour P,Acres RB,Kieny MP

    更新日期:2000-04-01 00:00:00

  • Application of RNA-sequencing to identify transcriptome modification by DCLK1 in colorectal cancer cells.

    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

    authors: Li L,Mei H,Commey ANA

    更新日期:2020-09-01 00:00:00

  • Tumor gene therapy by MVA-mediated expression of T-cell-stimulating antibodies.

    abstract::Immune responses to tumor-associated antigens are often dampened by a tumor-induced state of immune anergy. Previous work has attempted to overcome tumor-induced T-cell anergy by the direct injection of vectors carrying the genes encoding one of a variety of cytokines. We hypothesised that the polyclonal stimulation o...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700461

    authors: Paul S,Regulier E,Rooke R,Stoeckel F,Geist M,Homann H,Balloul JM,Villeval D,Poitevin Y,Kieny MP,Acres RB

    更新日期:2002-05-01 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

  • 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

  • Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells.

    abstract::Most advanced solid tumors metastasize to different organs. However, no gene therapy effective for multiple tumors has yet been developed. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehic...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7701079

    authors: Kanehira M,Xin H,Hoshino K,Maemondo M,Mizuguchi H,Hayakawa T,Matsumoto K,Nakamura T,Nukiwa T,Saijo Y

    更新日期:2007-11-01 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

  • Development of an oncolytic herpes simplex virus using a tumor-specific HIF-responsive promoter.

    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

    authors: Longo SL,Griffith C,Glass A,Shillitoe EJ,Post DE

    更新日期:2011-02-01 00:00:00

  • Alteration of drug chemosensitivity caused by the adenovirus-mediated transfer of the wild-type p53 gene in human lung cancer cells.

    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

    authors: Osaki S,Nakanishi Y,Takayama K,Pei XH,Ueno H,Hara N

    更新日期:2000-02-01 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

  • 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

  • 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

  • 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

  • Alternative splicing as a novel of means of regulating the expression of therapeutic genes.

    abstract::In order to determine the potential of alternative splicing as a means of targeting the expression of therapeutic genes to tumor cells in vivo, a series of episomal plasmid-based "splice-activated gene expression" (pSAGE) vectors was generated, which contain minigene cassettes composed of various combinations of the t...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700427

    authors: Hayes GM,Carpenito C,Davis PD,Dougherty ST,Dirks JF,Dougherty GJ

    更新日期:2002-02-01 00:00:00