Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses.


: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 Ad5 fiber knob with that from another adenovirus serotype 35 (Ad35); the resulting vector was designated MOA35. Here we evaluated the therapeutic efficacies of MOA5 and MOA35 for human osteosarcoma. Midkine mRNA expression and its promoter activity was significantly high in five human osteosarcoma cell lines, but was restricted in normal cells. Very low levels of adenovirus cellular receptor coxsackievirus/adenovirus receptor (CAR) (Ad5 receptor) expression were observed in MNNG-HOS and MG-63 cells, whereas high levels of CAR expression were seen in the other osteosarcoma cell lines. By contrast, CD46 (Ad35 receptor) was highly expressed in all osteosarcoma cell lines. Infectivity and in vitro cytocidal effect of MOA35 was significantly enhanced in MNNG-HOS and MG-63 cells compared with MOA5, although the cytocidal effects of MOA5 were sometimes higher in high CAR-expressing cell lines. In MG-63 xenograft models, MOA35 significantly enhanced antitumor effects compared with MOA5. Our findings indicate that MOA5 and MOA35 allow tailored virotherapy and facilitate more effective treatments for osteosarcoma.


Cancer Gene Ther


Cancer gene therapy


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




Has Abstract


2014-03-01 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


    authors: Walther W,Stein U,Fichtner I,Alexander M,Shoemaker RH,Schlag PM

    更新日期:2000-06-01 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

  • 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


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

    更新日期:2001-12-01 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


    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

  • 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


    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

  • Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.

    abstract::We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-ma...

    journal_title:Cancer gene therapy

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Finocchiaro LM,Glikin GC

    更新日期:2012-12-01 00:00:00

  • Cytokine-armed vaccinia virus infects the mesothelioma tumor microenvironment to overcome immune tolerance and mediate tumor resolution.

    abstract::Intratumoral (i.t.) administration of cytokine genes expressed by viral vectors represents a rational approach that induces cytokine secretion at the site they are needed, and i.t. vaccinia virus (VV) has shown promise in mesothelioma patients. However, we and others have shown that the mesothelioma tumor microenviron...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Jackaman C,Nelson DJ

    更新日期:2010-06-01 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

  • 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


    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

  • The incidence, genetic characteristics, and prognosis of leukemia with concurrent pathogenic fusion genes: a series of 25 cases from a large cohort of leukemia patients.

    abstract::Recurrent fusion genes (FGs) with clinical significances in leukemias are mainly mutually exclusive, and the coexistence of different FGs has been rarely reported. In this study, we retrospectively analyzed the incidence, genetic characteristics, and prognosis of leukemias with concurrent pathogenic FGs, which commonl...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Chen X,Wang F,Wang T,Zhang Y,Ma X,Yuan L,Teng W,Guo L,Liu M,Liu M,Chen J,Nie D,Zhang Y,Zhou X,Wang M,Chen KN,Zhu P,Liu H

    更新日期:2020-02-01 00:00:00

  • Depleting regulatory T cells with arginine-rich, cell-penetrating, peptide-conjugated morpholino oligomer targeting FOXP3 inhibits regulatory T-cell function.

    abstract::CD4+CD25+regulatory T cells (T(reg)) impair anti-tumor and anti-viral immunity. As there are higher T(reg) levels in cancer patients compared with healthy individuals, there is considerable interest in eliminating them or altering their function as part of cancer or viral immunotherapy strategies. The scurfin transcri...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Morse MA,Hobeika A,Serra D,Aird K,McKinney M,Aldrich A,Clay T,Mourich D,Lyerly HK,Iversen PL,Devi GR

    更新日期:2012-01-01 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


    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

  • 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


    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

  • Fusion protein from RGD peptide and Fc fragment of mouse immunoglobulin G inhibits angiogenesis in tumor.

    abstract::Targeting tumor vasculature represents an interesting approach for the treatment of solid tumors. The alpha v beta 3 integrins have been found to be specifically associated with angiogenesis in tumors. By using bacteriophage display technology, Ruoslahti et al found that a group of peptides containing the RGD (Arg-Gly...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Li J,Ji J,Holmes LM,Burgin KE,Barton LB,Yu X,Wagner TE,Wei Y

    更新日期:2004-05-01 00:00:00

  • Locked nucleic acid inhibits miR-92a-3p in human colorectal cancer, induces apoptosis and inhibits cell proliferation.

    abstract::MicroRNAs (miRNAs) are a type of small noncoding RNAs that have a vital role in basic biological processes such as cellular growth, division and apoptosis. A change in the expression of miRNAs can induce many diseases. Recently, the role of miRNA in some of the cancers as a tumor suppressor and oncogene has been recog...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Ahmadi S,Sharifi M,Salehi R

    更新日期:2016-07-01 00:00:00

  • Cancer gene therapy: an awkward adolescence.

    abstract::At the Eleventh International Conference on Gene Therapy of Cancer (December 12-14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审


    authors: Gottesman MM

    更新日期:2003-07-01 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


    authors: Batra RK,Berschneider H,Curiel DT

    更新日期:1994-09-01 00:00:00

  • Targeted-simultaneous expression of Gas1 and p53 using a bicistronic adenoviral vector in gliomas.

    abstract::The targeted expression of transgenes is one of the principal goals of gene therapy, and it is particularly relevant for the treatment of brain tumors. In this study, we examined the effect of the overexpression of human gas1 (growth arrest specific 1) and human p53 cDNAs, both under the transcriptional control of a p...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Benítez JA,Arregui L,Vergara P,Segovia J

    更新日期:2007-10-01 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


    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

  • 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


    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

  • Intravenous administration of adenoviruses targeting transforming growth factor beta signaling inhibits established bone metastases in 4T1 mouse mammary tumor model in an immunocompetent syngeneic host.

    abstract::We have examined the effect of adenoviruses expressing soluble transforming growth factor receptorII-Fc (sTGFβRIIFc) in a 4T1 mouse mammary tumor bone metastasis model using syngeneic BALB/c mice. Infection of 4T1 cells with a non-replicating adenovirus, Ad(E1-).sTβRFc, or with two oncolytic adenoviruses, Ad.sTβRFc an...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Zhang Z,Hu Z,Gupta J,Krimmel JD,Gerseny HM,Berg AF,Robbins JS,Du H,Prabhakar B,Seth P

    更新日期:2012-09-01 00:00:00

  • High expression of UBE2T predicts poor prognosis and survival in multiple myeloma.

    abstract::Multiple myeloma (MM) is one of hematological malignancies, characterized by malignant proliferation of plasma cells. Biomarkers play an important role in evaluating the development and prognosis of MM. Ubiquitin-conjugating enzyme E2T (UBE2T) is served to connect with particular E3 ubiquitin ligase to degraded-relate...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Zhang W,Zhang Y,Yang Z,Liu X,Yang P,Wang J,Hu K,He X,Zhang X,Jing H

    更新日期:2019-11-01 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


    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

  • 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


    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

  • Simultaneous inhibition of Rac1 and IKK pathways sensitizes lung cancer cells to TNFalpha-mediated apoptosis.

    abstract::Lung cancer is the most frequently occurring cancer in the world and causes more deaths in the United States than does colon, breast, and prostate cancer combined. Despite advances in treatment modalities including radiation, surgery, and chemotherapy, the overall survival in lung cancer remains low. The cytokine tumo...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Sanlioglu S,Luleci G,Thomas KW

    更新日期:2001-11-01 00:00:00

  • Phase I and biodistribution study of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene and ganciclovir administration in patients with head and neck cancer and other malignant tumors.

    abstract::In this study, we investigated the safety and efficacy in cancer patients of a single intra-tumor injection of recombinant adenovirus vector-mediated herpes simplex virus thymidine kinase gene (AdV/TK) followed by systemic administration of ganciclovir (GCV). In 18 patients with malignant tumors refractory to standard...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Xu F,Li S,Li XL,Guo Y,Zou BY,Xu R,Liao H,Zhao HY,Zhang Y,Guan ZZ,Zhang L

    更新日期:2009-09-01 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


    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

  • Regression of primary hepatocarcinoma in cancer-prone transgenic mice by local interferon-gamma delivery is associated with macrophages recruitment and nitric oxide production.

    abstract::The clinical potential of tumor therapies must be evaluated using animal models closely resembling human cancers. We investigated the impact of locally delivered interferon-gamma (IFN-gamma) on primary hepatocarcinoma spontaneously developed by T-SV40 transgenic mice. A single intratumor injection of adenovirus IFN-ga...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Baratin M,Ziol M,Romieu R,Kayibanda M,Gouilleux F,Briand P,Leroy P,Haddada H,Rénia L,Viguier M,Guillet JG

    更新日期:2001-03-01 00:00:00

  • Sustained cytokine production and immunophenotypic changes in human neuroblastoma cell lines transduced with a human gamma interferon vector.

    abstract::The majority of human neuroblastomas express low to undetectable levels of major histocompatibility complex (MHC) class I and II antigens (MHC-I and -II). We studied the effects of gamma interferon (gamma-IFN) transduction on expression of these antigens in six human neuroblastoma cell lines with and without genomic a...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Uçar K,Seeger RC,Challita PM,Watanabe CT,Yen TL,Morgan JP,Amado R,Chou E,McCallister T,Barber JR

    更新日期:1995-09-01 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


    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