Tumor-associated antigen/IL-21-transduced dendritic cell vaccines enhance immunity and inhibit immunosuppressive cells in metastatic melanoma.

Abstract:

:Dendritic cell (DC)-based vaccine approaches are being actively evaluated for developing immunotherapeutic agents against cancers. In this study, we investigated the use of engineered DCs expressing transgenic tumor-associated antigen hgp100 and the regulatory cytokine interleukin-21, namely DC-hgp100/mIL-21, as a therapeutic vaccine against melanoma. Tumor-bearing mice were injected intratumorally with transgenic DCs followed by three booster injections. Transgenic DC-hgp100/mIL-21 showed significant reduction in primary tumor growth and metastasis compared with DC-hgp100 alone and DC-mIL-21 alone. In vivo depletion of specific immune cell types (CD8(+) T, CD4(+) T and Natural killer (NK)-1.1(+) cells) effectively blocked the protective effect of this combinational vaccine. In adoptive transfer experiments, a survival rate of nearly 90% was observed at 60 days post-tumor inoculation for the combinational vaccine group. In contrast, all mice in the DC-hgp100 and DC-mIL-21-only groups died within 43-46 days after tumor challenge. Considerably increased levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, granulocyte macrophage colony-stimulating factor (GM-CSF) and cytotoxic T lymphocytes (CTLs) were detected with the combination vaccine group compared with other individual treatment groups. In comparison with the DC-hgp100 or mIL-21 groups, the combinational DC-hgp100/mIL-21 vaccine also drastically suppressed the myeloid-derived suppressor cells (MDSCs) and T-regulatory (Treg) cell populations. Our findings suggest that a combinational DC- and gene-based hgp100 and mIL-21 vaccine therapy strategy warrants further evaluation as a clinically relevant cancer vaccine approach for human melanoma patients.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Aravindaram K,Wang PH,Yin SY,Yang NS

doi

10.1038/gt.2014.12

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

457-67

issue

5

eissn

0969-7128

issn

1476-5462

pii

gt201412

journal_volume

21

pub_type

杂志文章
  • Potent antitumor activity of oncolytic adenovirus-mediated SOCS1 for hepatocellular carcinoma.

    abstract::Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse cancers, which contributes to the proliferation and survival of cancer cells by upregulating apoptosis inhibitors and cell cycle regulators. Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator of...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2012.4

    authors: Liu L,Li W,Wei X,Cui Q,Lou W,Wang G,Hu X,Qian C

    更新日期:2013-01-01 00:00:00

  • A novel magnetic approach to enhance the efficacy of cell-based gene therapies.

    abstract::Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. We have devised a novel way of using magnetic nanoparticles (MNPs) to enh...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2008.57

    authors: Muthana M,Scott SD,Farrow N,Morrow F,Murdoch C,Grubb S,Brown N,Dobson J,Lewis CE

    更新日期:2008-06-01 00:00:00

  • Restoration of all dystrophin protein interactions by functional domains in trans does not rescue dystrophy.

    abstract::Rescue of dystrophic skeletal muscle in mdx and utrophin/dystrophin-deficient (dko) mouse models by reintroduction of dystrophin has validated gene therapy as a potential therapeutic approach for Duchenne muscular dystrophy. However, the size of the dystrophin gene exceeds the capacity of adeno-associated viral (AAV) ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302686

    authors: Gardner KL,Kearney JA,Edwards JD,Rafael-Fortney JA

    更新日期:2006-05-01 00:00:00

  • Multi-subtype gp160 DNA immunization induces broadly neutralizing anti-HIV antibodies.

    abstract::A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulat...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302275

    authors: Rollman E,Hinkula J,Arteaga J,Zuber B,Kjerrström A,Liu M,Wahren B,Ljungberg K

    更新日期:2004-07-01 00:00:00

  • Lipofection of cultured mouse muscle cells: a direct comparison of Lipofectamine and DOSPER.

    abstract::Cationic lipid-DNA complexes (lipoplexes) have been widely used as gene transfer vectors which avoid the adverse immunogenicity and potential for viraemia of viral vectors. With the long-term aim of gene transfer into skeletal muscle in vivo, we describe a direct in vitro comparison of two commercially available catio...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300604

    authors: Dodds E,Dunckley MG,Naujoks K,Michaelis U,Dickson G

    更新日期:1998-04-01 00:00:00

  • Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina.

    abstract::Recombinant adeno-associated virus (rAAV) vectors are attractive candidates for the treatment of inherited and acquired retinal disease. Although rAAV vectors are well characterized in rodent models, a prerequisite to their clinical application in human patients is the thorough evaluation of their efficacy and safety ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301990

    authors: Bainbridge JW,Mistry A,Schlichtenbrede FC,Smith A,Broderick C,De Alwis M,Georgiadis A,Taylor PM,Squires M,Sethi C,Charteris D,Thrasher AJ,Sargan D,Ali RR

    更新日期:2003-08-01 00:00:00

  • Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection.

    abstract::Foamy virus (FV) vectors are promising for hematopoietic stem cell (HSC) gene therapy but preclinical data on the clonal composition of FV vector-transduced human repopulating cells is needed. Human CD34(+) human cord blood cells were transduced with an FV vector encoding a methylguanine methyltransferase (MGMT)P140K ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.20

    authors: Olszko ME,Adair JE,Linde I,Rae DT,Trobridge P,Hocum JD,Rawlings DJ,Kiem HP,Trobridge GD

    更新日期:2015-07-01 00:00:00

  • Potential therapeutic applications of recombinant, invasive E. coli.

    abstract::An invasive Escherichia coli expressing the inv gene from Yersinia pseudotuberculosis was used as a vector for protein delivery to mammalian epithelial cells. Upon incubation with beta1-integrin-expressing mammalian cells, the bacteria are internalized, allowing bacteria-encoded proteins to function from within the ma...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302281

    authors: Critchley RJ,Jezzard S,Radford KJ,Goussard S,Lemoine NR,Grillot-Courvalin C,Vassaux G

    更新日期:2004-08-01 00:00:00

  • Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector.

    abstract::One factor limiting the ability to modify human repopulating hematopoietic cells genetically with retroviral vectors is the relatively low expression of the cognate viral receptor. We have tested sequential transduction of human hematopoietic cells with an adenoviral vector encoding the ecotropic retroviral receptor f...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300974

    authors: Nathwani AC,Persons DA,Stevenson SC,Frare P,McClelland A,Nienhuis AW,Vanin EF

    更新日期:1999-08-01 00:00:00

  • Selective cell ablation in transgenic mice expression E. coli nitroreductase.

    abstract::The gene encoding E. coli nitroreductase (NTR) was expressed in the luminal cells of the mammary gland of transgenic mice using the ovine beta-lactoglobulin promoter. Treatment of NTR expressing animals with the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) resulted in a rapid and selective killing of this pop...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300367

    authors: Clark AJ,Iwobi M,Cui W,Crompton M,Harold G,Hobbs S,Kamalati T,Knox R,Neil C,Yull F,Gusterson B

    更新日期:1997-02-01 00:00:00

  • Articular cartilage repair by genetically modified bone marrow aspirate in sheep.

    abstract::Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was p...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.16

    authors: Ivkovic A,Pascher A,Hudetz D,Maticic D,Jelic M,Dickinson S,Loparic M,Haspl M,Windhager R,Pecina M

    更新日期:2010-06-01 00:00:00

  • Intrabody-mediated phenotypic knockout of major histocompatibility complex class I expression in human and monkey cell lines and in primary human keratinocytes.

    abstract::Cultured keratinocyte allografts from unrelated donors can be readily grown as sheets in large-scale cell culture and have been used as an immediate skin cover for severely burned patients. Despite the absence of passenger leukocytes and the unlimited amount of material that can be obtained for permanent skin coverage...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301656

    authors: Mhashilkar AM,Doebis C,Seifert M,Busch A,Zani C,Soo Hoo J,Nagy M,Ritter T,Volk HD,Marasco WA

    更新日期:2002-03-01 00:00:00

  • The immunogenicity of virus-derived 2A sequences in immunocompetent individuals.

    abstract::Genetic engineering of T cells for adoptive immunotherapy in cancer patients has shown significant promise. To ensure optimal antitumor activity and safety, the simultaneous expression of multiple genes is frequently required, and short viral-derived 2A sequences are increasingly preferred for this purpose. Concerns e...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2013.25

    authors: Arber C,Abhyankar H,Heslop HE,Brenner MK,Liu H,Dotti G,Savoldo B

    更新日期:2013-09-01 00:00:00

  • Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded AAV9-GFP for gene therapy of neurological disorders.

    abstract::Adeno-associated virus (AAV) gene therapy constitutes a powerful tool for the treatment of neurodegenerative diseases. While AAVs are generally administered systemically to newborns in preclinical studies of neurological disorders, in adults the maturity of the blood-brain barrier (BBB) must be considered when selecti...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2017.18

    authors: Bey K,Ciron C,Dubreil L,Deniaud J,Ledevin M,Cristini J,Blouin V,Aubourg P,Colle MA

    更新日期:2017-05-01 00:00:00

  • Evaluation of recombinant alphaviruses as vectors in gene therapy.

    abstract::Alphavirus vectors based on Sindbis virus and Semliki Forest virus (SFV) were characterized as potential gene transfer vectors. Initial studies were performed using vectors engineered to transfer either lacZ or green fluorescent protein (GFP). High levels of gene transfer were achieved in human primary fibroblasts, BH...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301122

    authors: Wahlfors JJ,Zullo SA,Loimas S,Nelson DM,Morgan RA

    更新日期:2000-03-01 00:00:00

  • Enhanced transduction of mouse salivary glands with AAV5-based vectors.

    abstract::We previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in salivary gland cells in vitro and in vivo. However, it is not known how other rAAV serotypes perform when infused into salivary glands. The capsids of serotypes 4 and 5 are distinct...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302691

    authors: Katano H,Kok MR,Cotrim AP,Yamano S,Schmidt M,Afione S,Baum BJ,Chiorini JA

    更新日期:2006-04-01 00:00:00

  • An adenovirus vector with a chimeric fiber incorporating stabilized single chain antibody achieves targeted gene delivery.

    abstract::Adenovirus (Ad) vectors are of utility for many therapeutic applications. Strategies have been developed to alter adenoviral tropism to achieve a cell-specific gene delivery capacity employing fiber modifications allowing genetic incorporation of targeting motifs. In this regard, single chain antibodies (scFv) represe...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302603

    authors: Hedley SJ,Auf der Maur A,Hohn S,Escher D,Barberis A,Glasgow JN,Douglas JT,Korokhov N,Curiel DT

    更新日期:2006-01-01 00:00:00

  • The bystander effect in the HSVtk/ganciclovir system and its relationship to gap junctional communication.

    abstract::The bystander effect (BSE) is an interesting and important property of the herpes thymidine kinase/ganciclovir (hTK/GCV) system of gene therapy for cancer. With the BSE, not only are the hTK expressing cells killed upon ganciclovir (GCV) exposure but also neighboring wild-type tumor cells. On testing a large number of...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300784

    authors: Touraine RL,Ishii-Morita H,Ramsey WJ,Blaese RM

    更新日期:1998-12-01 00:00:00

  • RNA interference in embryonic stem cells and the prospects for future therapies.

    abstract::In 1998, two distinct and exciting scientific fields emerged which have profoundly shaped the current direction of biomedical research. The discovery of RNA interference (RNAi) and the derivation of human embryonic stem (ES) cells have yielded exciting new possibilities for researchers and clinicians alike. While fund...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302723

    authors: Heidersbach A,Gaspar-Maia A,McManus MT,Ramalho-Santos M

    更新日期:2006-03-01 00:00:00

  • Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma.

    abstract::Gene therapy with Plasmid AMEP (antiangiogenic metargidin peptide) has recently been studied as a potential targeted therapy for melanoma. This plasmid is designed to downregulate α5β1 and αvβ3 integrins. In our study, electroporation was used as a nonviral delivery system. We investigated the antiangiogenic and direc...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2015.26

    authors: Bosnjak M,Dolinsek T,Cemazar M,Kranjc S,Blagus T,Markelc B,Stimac M,Zavrsnik J,Kamensek U,Heller L,Bouquet C,Turk B,Sersa G

    更新日期:2015-07-01 00:00:00

  • Gamma-irradiation enhances transgene expression in leukemic cells.

    abstract::The majority of immunotherapy-based gene therapy protocols consist of ex vivo gene transfer in tumor cells. To prevent further in vivo growth, modified cells must be irradiated before reinjection into patients. The present study examines the effects of gamma-irradiation on transgene expression in transduced leukemic c...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301870

    authors: Vereecque R,Saudemont A,Wickham TJ,Gonzalez R,Hetuin D,Fenaux P,Quesnel B

    更新日期:2003-02-01 00:00:00

  • Effective treatment of vascular endothelial growth factor refractory hindlimb ischemia by a mutant endothelial nitric oxide synthase gene.

    abstract::Gene delivery of angiogenic growth factors is a promising approach for the treatment of ischemic cardiovascular diseases. However, success of this new therapeutic principle is hindered by the lack of critical understanding as to how disease pathology affects the efficiency of gene delivery and/or the downstream signal...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302781

    authors: Qian HS,Liu P,Huw LY,Orme A,Halks-Miller M,Hill SM,Jin F,Kretschmer P,Blasko E,Cashion L,Szymanski P,Vergona R,Harkins R,Yu J,Sessa WC,Dole WP,Rubanyi GM,Kauser K

    更新日期:2006-09-01 00:00:00

  • Adenovirus-mediated apo(a)-antisense-RNA expression efficiently inhibits apo(a) synthesis in vitro and in vivo.

    abstract::Apo(a) is a very atherogenic plasma protein without apparent function, which is highly expressed in humans. The variation in plasma Lp(a) concentration among individuals is considerable. Approximately 10-15% of the white population exhibit plasma Lp(a) concentrations above the atherogenic cut-off value of approximatel...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301434

    authors: Frank S,Gauster M,Strauss J,Hrzenjak A,Kostner GM

    更新日期:2001-03-01 00:00:00

  • GCV phosphates are transferred between HeLa cells despite lack of bystander cytotoxicity.

    abstract::The role of gap junctional intercellular communication (GJIC) in bystander killing with herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) was evaluated in U251 cells expressing a dominant-negative connexin 43 cDNA (DN14), and in HeLa cells, reportedly devoid of connexin protein. These cell lines bot...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302487

    authors: Gentry BG,Im M,Boucher PD,Ruch RJ,Shewach DS

    更新日期:2005-07-01 00:00:00

  • Particle-mediated gene transfer into murine livers using a newly developed gene gun.

    abstract::Although particle-mediated gene transfer using gene gun technology has been applied for gene transfer into epidermis, applications of this technology to visceral tissues have not been well investigated. Although all helium gas-driven gene gun instruments have used macrocarriers to discharge DNA-coated microprojectiles...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301192

    authors: Kuriyama S,Mitoro A,Tsujinoue H,Nakatani T,Yoshiji H,Tsujimoto T,Yamazaki M,Fukui H

    更新日期:2000-07-01 00:00:00

  • In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes.

    abstract::Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 (Ex4) have displayed potent glucose homeostasis-modulating characteristics in type 2 diabetes (T2D). However, there are few reports of effectiveness in type 1 diabetes (T1D) therapy, where there is massive loss of beta cells. We previously described a novel GL...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302944

    authors: Soltani N,Kumar M,Glinka Y,Prud'homme GJ,Wang Q

    更新日期:2007-06-01 00:00:00

  • Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap.

    abstract::Retroviral vectors have become the primary tool for gene delivery into hematopoietic cells, including T lymphocytes. Lentiviral vectors offer an advantage over Moloney murine leukemia virus (MuLV) vectors because of their ability to translocate across an intact nuclear membrane and integrate into the genome of nonprol...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301378

    authors: Dardalhon V,Herpers B,Noraz N,Pflumio F,Guetard D,Leveau C,Dubart-Kupperschmitt A,Charneau P,Taylor N

    更新日期:2001-02-01 00:00:00

  • Pseudotyping of Moloney leukemia virus-based retroviral vectors with simian immunodeficiency virus envelope leads to targeted infection of human CD4+ lymphoid cells.

    abstract::In view of our recent findings that a truncated form of the envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) was efficiently incorporated into MoMLV particles, we studied the generation of Moloney murine leukemia virus (MoMLV)/simian immunodeficiency virus (SIV) pseudotypes. Unlike HIV-1, bot...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300603

    authors: Indraccolo S,Minuzzo S,Feroli F,Mammano F,Calderazzo F,Chieco-Bianchi L,Amadori A

    更新日期:1998-02-01 00:00:00

  • Intercellular trafficking and enhanced in vivo antitumour activity of a non-virally delivered P27-VP22 fusion protein.

    abstract::VP22, a structural protein from herpes simplex virus type I, exhibits the unique property of intercellular trafficking. This protein is exported from primary expressing cells and subsequently imported into neighbouring cells. This property is conserved when VP22 is genetically fused to a protein, making it a promising...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301904

    authors: Zavaglia D,Favrot MC,Eymin B,Tenaud C,Coll JL

    更新日期:2003-02-01 00:00:00

  • Efficient delivery of triplex forming oligonucleotides to tumor cells by adenovirus-polylysine complexes.

    abstract::Oligonucleotides (ODNs) show great promise in their ability to specifically inhibit single gene expression but must cross the cell membrane, escape the endosomal vesicle, and possibly traverse the nuclear membrane to arrive at their intracellular target molecules. In an attempt to improve the delivery of phosphodieste...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Ebbinghaus SW,Vigneswaran N,Miller CR,Chee-Awai RA,Mayfield CA,Curiel DT,Miller DM

    更新日期:1996-04-01 00:00:00