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 vehicle of gene therapy for targeting multiple tumors. First, we confirmed that mouse MSCs preferentially migrate to multiple tumors of the lung in the Colon-26 (C-26) lung metastasis model. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF), by an adenoviral vector with an RGD motif. MSCs expressing NK4 (NK4-MSCs) strongly inhibited development of lung metastases in the C-26 lung metastasis model after systemic administration via a tail vein. Treatment with NK4-MSCs significantly prolonged survival of the C-26-tumor-bearing mice by inhibiting tumor-associated angiogenesis and lymphangiogenesis and inducing apoptosis of the tumor cells. MSC-based gene therapy did not induce the severe adverse effects induced by conventional adenoviral vectors. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting multiple lung metastatic tumors.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

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

doi

10.1038/sj.cgt.7701079

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

894-903

issue

11

eissn

0929-1903

issn

1476-5500

pii

7701079

journal_volume

14

pub_type

杂志文章
  • Enhanced tumor suppression by an ING4/IL-24 bicistronic adenovirus-mediated gene cotransfer in human non-small cell lung cancer cells.

    abstract::ING4 as a member of inhibitor of growth (ING) tumor suppressor family has potent inhibitory effects on a variety of tumors. Interleukin-24 (IL-24), a cytokine-tumor suppressor, also shows broad-spectrum and tumor-specific antitumor activities. In this report, we constructed an ING4/IL-24 bicistronic adenovirus (Ad-ING...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.31

    authors: Zhu Y,Lv H,Xie Y,Sheng W,Xiang J,Yang J

    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

    doi:10.1038/cgt.2017.8

    authors: Liu HY,Zhang CJ

    更新日期:2017-06-01 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

  • Downmodulation of bFGF-binding protein expression following restoration of p53 function.

    abstract::Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector-mediated wild-type p53 transduction results in growth inhibition of squamous cell carcinoma ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700361

    authors: Sherif ZA,Nakai S,Pirollo KF,Rait A,Chang EH

    更新日期:2001-10-01 00:00:00

  • Effectiveness of three ribozymes for cleavage of an RNA transcript from human papillomavirus type 18.

    abstract::We tested three hammerhead ribozymes for their ability to bind and cleave RNA transcripts derived from the E6 and E7 genes of human papillomavirus (HPV) type-18. Targets were located at nucleotides (nt) 123, 309, and 671 of the viral transcript. In vitro each ribozyme hybridized to its target site when the ribozyme:ta...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Chen Z,Kamath P,Zhang S,Weil MM,Shillitoe EJ

    更新日期:1995-12-01 00:00:00

  • Inhibition of Gli2 suppresses tumorigenicity in glioblastoma stem cells derived from a de novo murine brain cancer model.

    abstract::The prognosis of glioblastoma remains poor despite intensive research efforts. Glioblastoma stem cells (GSCs) contribute to tumorigenesis, invasive capacity, and therapy resistance. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a stem cell marker, is involved in the maintenance of GSCs, although ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-020-00282-5

    authors: Tanigawa S,Fujita M,Moyama C,Ando S,Ii H,Kojima Y,Fujishita T,Aoki M,Takeuchi H,Yamanaka T,Takahashi Y,Hashimoto N,Nakata S

    更新日期:2021-01-07 00:00:00

  • Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase.

    abstract::A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 ce...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Li Z,Shanmugam N,Katayose D,Huber B,Srivastava S,Cowan K,Seth P

    更新日期:1997-03-01 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

  • Human growth hormone gene transfer into tumor cells may improve cancer chemotherapy.

    abstract::Chemotherapy remains the main tool for the treatment of cancers, but is often hampered by tumor cell resistance. In this context, the transfer of genes able to accentuate the effect of anticancer drugs may constitute a useful approach, as exemplified by inactivation of nuclear factor (NF)-kappa B via direct transfer o...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700467

    authors: Cherbonnier C,Déas O,Vassal G,Merlin JL,Haeffner A,Senik A,Charpentier B,Dürrbach A,Bénard J,Hirsch F

    更新日期:2002-06-01 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

  • Identification of transcription factors (TFs) and targets involved in the cholangiocarcinoma (CCA) by integrated analysis.

    abstract::The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integr...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2016.64

    authors: Yang L,Feng S,Yang Y

    更新日期:2016-12-01 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

  • 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

  • Therapeutic efficacy of T cells derived from lymph nodes draining a poorly immunogenic tumor transduced to secrete granulocyte-macrophage colony-stimulating factor.

    abstract::We examined the host immune response to the poorly immunogenic B16-BL6 melanoma, which was transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) (450 ng/10(6)/24 h). Tumor growth after subcutaneous inoculation was not significantly altered, although an influx of neutrophils and monocytes/macr...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Arca MJ,Krauss JC,Aruga A,Cameron MJ,Shu S,Chang AE

    更新日期:1996-01-01 00:00:00

  • Anticancer activity of oncolytic adenovirus vector armed with IFN-alpha and ADP is enhanced by pharmacologically controlled expression of TRAIL.

    abstract::We have previously described oncolytic adenovirus (Ad) vectors KD3 and KD3-interferon (IFN) that were rendered cancer-specific by mutations in the E1A region of Ad; these mutations abolish binding of E1A proteins to p300/CBP and pRB. The antitumor activity of the vectors was enhanced by overexpression of the Adenoviru...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7701107

    authors: Shashkova EV,Kuppuswamy MN,Wold WS,Doronin K

    更新日期:2008-02-01 00:00:00

  • 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 ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700967

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

    更新日期:2006-10-01 00:00:00

  • Adenovirus-mediated N5 gene transfer inhibits tumor cell proliferation by induction of apoptosis.

    abstract::Gene therapy designed to initiate apoptotic cell death provides a potentially effective method to treat cancer. A prerequisite for this approach is the identification of genes that function in distinct apoptotic pathways. Although apoptotic pathways initiated by receptors such as tumor necrosis factor receptor-1 are w...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700194

    authors: Yin S,Hung MC,Goodrich DW

    更新日期:2000-07-01 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

  • 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

  • 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

    doi:10.1038/sj.cgt.7700762

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

    更新日期:2004-12-01 00:00:00

  • Induction of antitumor immunity by combined immunogene therapy using IL-2 and IL-12 in low antigenic Lewis lung carcinoma.

    abstract::Interleukin-2 (IL-2) and interleukin-12 (IL-12) are crucial cytokines that induce potent antitumor responses in a variety of animal cancer models. Although single gene transfer of either IL-2 or IL-12 exhibits limited antitumor effects, the combination of IL-2 and IL-12 has been shown to induce a stronger antitumor re...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700251

    authors: Tanaka M,Saijo Y,Sato G,Suzuki T,Tazawa R,Satoh K,Nukiwa T

    更新日期:2000-11-01 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

  • 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

  • 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

  • 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

  • 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

  • T-cell-dependent antitumor effects produced by CD40 ligand expressed on mouse lung carcinoma cells are linked with the maturation of dendritic cells and secretion of a variety of cytokines.

    abstract::CD40/CD40 ligand (CD40L) interaction plays an essential role in cell-mediated immune responses. We examined whether expression of CD40L in murine lung carcinoma (A11) cells could produce antitumor effects. The proliferation rate in vitro of A11 cells transfected with the murine CD40L gene (A11/CD40L) was not different...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700584

    authors: Tada Y,O-Wang J,Yu L,Shimozato O,Wang YQ,Takiguchi Y,Tatsumi K,Kuriyama T,Takenaga K,Sakiyama S,Tagawa M

    更新日期:2003-06-01 00:00:00

  • Decidua mesenchymal stem cells migrated toward mammary tumors in vitro and in vivo affecting tumor growth and tumor development.

    abstract::Mesenchymal stem cells (MSCs) have affinity to tumor sites where they home, affecting their biology and growth. Previously, we have isolated mesenchymal cells from the decidua of the human placenta named as decidua-derived MSCs (DMSCs). The aims of the present study were to investigate the migration capacity of DMSCs ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2012.71

    authors: Vegh I,Grau M,Gracia M,Grande J,de la Torre P,Flores AI

    更新日期:2013-01-01 00:00:00

  • Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation.

    abstract::Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bc...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700673

    authors: Rosser CJ,Tanaka M,Pisters LL,Tanaka N,Levy LB,Hoover DC,Grossman HB,McDonnell TJ,Kuban DA,Meyn RE

    更新日期:2004-04-01 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