Bone marrow-derived cells as carriers of recombinant immunomodulatory cytokine genes to lymphoid organs.

Abstract:

:The purpose of this study was to determine the feasibility of cytokine gene delivery to lymphatic tissue using transduced bone marrow-derived cells. MBAE and pBABE retroviral vectors carrying the genes for murine interleukin-4 and the selection marker neomycin phosphotransferase (neo) were used to transduce bone marrow-derived dendritic cells (DC) and hematopoietic stem cells (HSC). A transduction efficiency of 11-33% for HSC and 2-10% for DC was achieved. Transduced HSC and DC released 55-170 pg of recombinant interleukin-4 per 1 x 10(6) cells/mL in vitro. To study the migration of the cells in vivo, we introduced the transduced cells into syngenic mice. DC were injected subcutaneously into the front limbs of unconditioned mice and HSC were intravenously administered to irradiated mice. The distribution of the transduced cells was studied by quantitative polymerase chain reaction for the neo gene as a marker. After 3 days, DC migrated to the axillary lymph nodes in the drainage area of the injection site and were detectable up to 5 days. After intravenous administration of transduced HSC, the neo gene could be found in up to 100 copies/5 x 10(3) cells in mesenterial lymph node, spleen, bone marrow, thymus, and liver. The distribution of the transduced cells was heterogenous: in different mice, different organs showed high copies of the neo gene after 10 and 13 days. After 39 days, two of three mice were negative for neo in all organs analyzed. In conclusion, bone marrow-derived cells can be genetically engineered ex vivo to deliver recombinant cytokine genes to lymphoid organs in vivo. In particular, DC might be candidate cells for use in immunomodulatory gene therapy for autoimmune diseases and cancer.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Fiehn C,Wettschureck N,Krauthoff A,Haas R,Ho AD

doi

10.1038/sj.cgt.7700204

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

1105-12

issue

8

eissn

0929-1903

issn

1476-5500

journal_volume

7

pub_type

杂志文章
  • 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

    doi:10.1038/sj.cgt.7700602

    authors: Gottesman MM

    更新日期:2003-07-01 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

  • 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

  • Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA.

    abstract::Breast cancer is the most common cause of cancer-related death worldwide, thus remaining a crucial health problem among women despite advances in conventional therapy. Therefore, new alternative strategies are needed for effective diagnosis and treatment. One approach is the use of oncolytic viruses for gene-directed ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.49

    authors: Seubert CM,Stritzker J,Hess M,Donat U,Sturm JB,Chen N,von Hof JM,Krewer B,Tietze LF,Gentschev I,Szalay AA

    更新日期:2011-01-01 00:00:00

  • PiggyBac as a novel vector in cancer gene therapy: current perspective.

    abstract::Selection of suitable delivery system is one of the crucial aspects in gene therapy that determines the efficiency of gene therapy. The past two decades have witnessed extensive efforts for finding safe and efficient vectors to overcome the limitations of viral vectors. The utilization of DNA transposon-based vectors ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2015.68

    authors: Mirzaei H,Sahebkar A,Jaafari MR,Hadjati J,Javanmard SH,Mirzaei HR,Salehi R

    更新日期:2016-02-01 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

  • E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells.

    abstract::Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700739

    authors: Rao XM,Tseng MT,Zheng X,Dong Y,Jamshidi-Parsian A,Thompson TC,Brenner MK,McMasters KM,Zhou HS

    更新日期:2004-09-01 00:00:00

  • Development of a novel adenovirus-alphavirus hybrid vector with RNA replicon features for malignant hematopoietic cell transduction.

    abstract::To improve the expression levels of transgenes in malignant hematopoietic cells, we developed a novel adenoviral-alphavirus hybrid vector Ad5/F11p-SFV-GFP that contains a Semliki Forest Virus (SFV) replicon and chimeric fibers of Ad5 and Ad11p. Ad5/F11p-SFV-GFP infected >95% of K562, U937 or Jurkat cells and 23.65% of...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2013.37

    authors: Yang Y,Xiao F,Lu Z,Li Z,Zuo H,Zhang Q,Li Q,Wang H,Wang LS

    更新日期:2013-08-01 00:00:00

  • Induction of CAMEL/NY-ESO-ORF2-specific CD8+ T cells upon stimulation with dendritic cells infected with a modified Ad5 vector expressing a chimeric Ad5/35 fiber.

    abstract::Delivery of the full-length tumor antigen might be more successful in immunotherapy than single peptides and has the advantage that patients no longer need to be selected for their HLA type. In this study, we tested the in vitro induction of CAMEL/NY-ESO-ORF2-specific T cells by dendritic cells infected with an adenov...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700674

    authors: Slager EH,van der Minne CE,Goudsmit J,van Oers JM,Kostense S,Havenga MJ,Osanto S,Griffioen M

    更新日期:2004-03-01 00:00:00

  • Oral contrast enhances the resolution of in-life NIS reporter gene imaging.

    abstract::Sodium iodide symporter (NIS) reporter gene imaging is an excellent technology for noninvasive cell fate determination in living animals unless the NIS-transduced cells reside in perigastric organs such as the spleen, liver, diaphragm, omentum, pancreas, perigastric lymph nodes or perigastric tumor deposits. Here we r...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2013.57

    authors: Suksanpaisan L,Pham L,McIvor S,Russell SJ,Peng KW

    更新日期:2013-11-01 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

    doi:10.1038/cgt.2009.19

    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

  • A qualitative transcriptional signature for determining the grade of colorectal adenocarcinoma.

    abstract::Histological grading (HG) is an important prognostic factor of colorectal adenocarcinoma (CRAC): the high-grade CRAC patients have poorer prognosis after tumor resection. Especially, the high-grade stage II CRAC patients are recommended to receive adjuvant chemotherapy. Due to the subjective nature of HG assessment, i...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-019-0139-1

    authors: Zheng H,Song K,Fu Y,You T,Yang J,Guo W,Wang K,Jin L,Gu Y,Qi L,Zhao W,Guo Z

    更新日期:2020-09-01 00:00:00

  • Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects.

    abstract::We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected int...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700630

    authors: Ugai S,Shimozato O,Yu L,Wang YQ,Kawamura K,Yamamoto H,Yamaguchi T,Saisho H,Sakiyama S,Tagawa M

    更新日期:2003-10-01 00:00:00

  • Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study.

    abstract::Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.4

    authors: García-Castro J,Alemany R,Cascalló M,Martínez-Quintanilla J,Arriero Mdel M,Lassaletta A,Madero L,Ramírez M

    更新日期:2010-07-01 00:00:00

  • Genetically marking human cells--results of the first clinical gene transfer studies.

    abstract::The rapid development of both knowledge and techniques in molecular biology have made it possible to engineer genetic constructs and transfer them into cells of individuals with various diseases. Such gene therapies may alleviate or perhaps even cure diseases for which no adequate treatment now exists. One potential a...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:

    authors: Cai Q,Rubin JT,Lotze MT

    更新日期:1995-06-01 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

  • Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model.

    abstract::Ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. The present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23H1 expression through adeno-associated virus (AAV)-mediated gene transfer. ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700899

    authors: Li J,Zhou J,Chen G,Wang H,Wang S,Xing H,Gao Q,Lu Y,He Y,Ma D

    更新日期:2006-03-01 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

  • Oncolytic adenovirus retargeted to Delta-EGFR induces selective antiglioma activity.

    abstract::The fact that glioblastomas, which are one of the most devastating cancers, frequently express the Delta-EGFR (epithelial growth factor receptor) also called mutant variant III of EGFR (EGFRvIII) suggests that this cancer cell-specific receptor might serve as an ideal target for cancer therapy. To assess its potential...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2008.75

    authors: Piao Y,Jiang H,Alemany R,Krasnykh V,Marini FC,Xu J,Alonso MM,Conrad CA,Aldape KD,Gomez-Manzano C,Fueyo J

    更新日期:2009-03-01 00:00:00

  • Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors.

    abstract::Interleukin-10 (IL-10) is a T helper type 2 (Th2) cytokine that suppresses Th1-mediated, cell-mediated immune responses and reciprocally enhances antibody-mediated responses. Previous studies, however, demonstrated that forced expression of the IL-10 gene in tumor cells could unexpectedly produce antitumor effects. We...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700418

    authors: Kawamura K,Bahar R,Natsume W,Sakiyama S,Tagawa M

    更新日期:2002-01-01 00:00:00

  • Oncolysis and suppression of tumor growth by a GFP-expressing oncolytic adenovirus controlled by an hTERT and CMV hybrid promoter.

    abstract::One of the challenges of oncolytic virotherapy is the inability to easily track or monitor virus activity during treatment. Here we describe the construction and functional characterization of Ad/hTC-GFP-E1, an oncolytic virus whose transgenes GFP and E1A are both under the control of a synthetic promoter (hTC). This ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700944

    authors: Davis JJ,Wang L,Dong F,Zhang L,Guo W,Teraishi F,Xu K,Ji L,Fang B

    更新日期:2006-07-01 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

  • Manufacture of T cells using the Sleeping Beauty system to enforce expression of a CD19-specific chimeric antigen receptor.

    abstract::T cells can be reprogrammed to redirect specificity to tumor-associated antigens (TAAs) through the enforced expression of chimeric antigen receptors (CARs). The prototypical CAR is a single-chain molecule that docks with TAA expressed on the cell surface and, in contrast to the T-cell receptor complex, recognizes tar...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/cgt.2014.69

    authors: Singh H,Moyes JS,Huls MH,Cooper LJ

    更新日期:2015-03-01 00:00:00

  • Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis.

    abstract::Melanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-020-00274-5

    authors: Chen XJ,Liu S,Han DM,Han DZ,Sun WJ,Zhao XC

    更新日期:2020-12-14 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

  • Adenovirus-mediated p16INK4 gene transfer significantly suppresses human breast cancer growth.

    abstract::The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancer...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700226

    authors: Campbell I,Magliocco A,Moyana T,Zheng C,Xiang J

    更新日期:2000-09-01 00:00:00

  • Amplification of the lytic potential of effector/memory CD8+ cells by vector-based enhancement of ICAM-1 (CD54) in target cells: implications for intratumoral vaccine therapy.

    abstract::We demonstrated that enhanced expression of the costimulatory molecules CD80, CD54 and CD48 (designated rF-TRICOM) on target cells, as delivered via a recombinant fowlpox vector, results in an increased state of stimulation of CD8+ T cells, and consequent increased lysis of target cells. CTL studies in conjunction wit...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700741

    authors: Slavin-Chiorini DC,Catalfamo M,Kudo-Saito C,Hodge JW,Schlom J,Sabzevari H

    更新日期:2004-10-01 00:00:00

  • Employment of microarray analysis to characterize biologic differences associated with tropism-modified adenoviral vectors: utilization of non-native cellular entry pathways.

    abstract::In this study, we have applied high-density oligonucleotide microarray technology to characterize biologic changes associated with adenoviral vector-mediated target cell infection. We infected a human melanoma cell line, M21, with the tropism-modified vectors, Ad5lucRGD and Ad5/3luc1. In addition, we infected the M21 ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700776

    authors: Volk AL,Rivera AA,Page GP,Salazar-Gonzalez JF,Nettelbeck DM,Matthews QL,Curiel DT

    更新日期:2005-02-01 00:00:00

  • E1A, E1B double-restricted replicative adenovirus at low dose greatly augments tumor-specific suicide gene therapy for gallbladder cancer.

    abstract::Combination therapy with replicative oncolytic viruses is a recent topic in innovative cancer therapy, but few studies have examined the efficacy of oncolytic adenovirus plus replication-deficient adenovirus carrying a suicide gene. We aim to evaluate whether an E1A, E1B double-restricted oncolytic adenovirus, AxdAdB-...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2008.67

    authors: Fukuda K,Abei M,Ugai H,Kawashima R,Seo E,Wakayama M,Murata T,Endo S,Hamada H,Hyodo I,Yokoyama KK

    更新日期:2009-02-01 00:00:00

  • Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus.

    abstract::Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700732

    authors: Lim HY,Ahn M,Chung HC,Gardner TA,Kao C,Lee SJ,Kim SJ

    更新日期:2004-08-01 00:00:00