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


: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.


Gene Ther


Gene therapy


Aravindaram K,Wang PH,Yin SY,Yang NS




Has Abstract


2014-05-01 00:00:00














  • Understanding lentiviral vector chromatin targeting: working to reduce insertional mutagenic potential for gene therapy.

    abstract::Replication-deficient retroviruses have been successfully utilized as vectors, offering an efficient, stable method of therapeutic gene delivery. Many examples exist proving this mode of integrative gene transfer is both effective and safe in cultured systems and clinical trials. Along with their success, severe side ...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审


    authors: Papayannakos C,Daniel R

    更新日期:2013-06-01 00:00:00

  • Incorporation of beta-globin untranslated regions into a Sindbis virus vector for augmentation of heterologous mRNA expression.

    abstract::Polynucleotide immunization has been employed as a means of inducing immune responses through the introduction of antigen-encoding DNA. While immunization against specific tumor antigens may be achieved through this strategy, various candidate tumor antigens may not be approached via DNA-based vaccines as they represe...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Strong TV,Hampton TA,Louro I,Bilbao G,Conry RM,Curiel DT

    更新日期:1997-06-01 00:00:00

  • The relevance of coagulation factor X protection of adenoviruses in human sera.

    abstract::Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined th...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Duffy MR,Doszpoly A,Turner G,Nicklin SA,Baker AH

    更新日期:2016-07-01 00:00:00

  • New tools for the generation of E1- and/or E3-substituted adenoviral vectors.

    abstract::We have designed new vectors for the construction of recombinant adenoviruses containing expression cassettes in the E1 and/or E3 regions. Using a versatile set of restriction enzymes, the cassettes are cloned into small bacterial vectors and subsequently introduced into large plasmids containing the adenoviral sequen...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Danthinne X,Werth E

    更新日期:2000-01-01 00:00:00

  • Simultaneous targeted alteration of the tyrosinase and c-kit genes by single-stranded oligonucleotides.

    abstract::We have shown that various forms of oligonucleotides, chimeric RNA-DNA oligonucleotide (RDO) and single-stranded oligodeoxynucleotide (ODN), are capable of chromosomal gene alterations in mammalian cells. Using two ODNs we corrected an inactivating mutation in the tyrosinase gene and introduced an activating mutation ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Alexeev V,Igoucheva O,Yoon K

    更新日期:2002-12-01 00:00:00

  • Angiogenic and antiangiogenic gene therapy.

    abstract::Gene therapy is thought to be a promising method for the treatment of various diseases. One gene therapy strategy involves the manipulations on a process of formation of new vessels, commonly defined as angiogenesis. Angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of cardiovas...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审


    authors: Malecki M,Kolsut P,Proczka R

    更新日期:2005-10-01 00:00:00

  • Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium tuberculosis.

    abstract::Active disease of tuberculosis (TB) can be developed decades later by either a relapse of the initial infection (endogenous reactivation) or by an entrance of the secondary infection (exogenous reinfection), since the current chemotherapy cannot lead to complete elimination of tuberculosis. Although the immunotherapeu...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Ha SJ,Jeon BY,Youn JI,Kim SC,Cho SN,Sung YC

    更新日期:2005-04-01 00:00:00

  • Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA.

    abstract::RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and unifor...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Chen CC,Ko TM,Ma HI,Wu HL,Xiao X,Li J,Chang CM,Wu PY,Chen CH,Han JM,Yu CP,Jeng KS,Hu CP,Tao MH

    更新日期:2007-01-01 00:00:00

  • Evaluation of prenatal intra-amniotic LAMB3 gene delivery in a mouse model of Herlitz disease.

    abstract::Prenatal gene therapy has been considered for Herlitz junctional epidermolysis bullosa (H-JEB), a lethal genodermatosis caused by the absence of any of the three subunits of laminin-5, resulting from birth in widespread blistering and erosions of skin and mucosae. To investigate this strategy in an animal model, adeno...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Mühle C,Neuner A,Park J,Pacho F,Jiang Q,Waddington SN,Schneider H

    更新日期:2006-12-01 00:00:00

  • T cell activation with systemic agonistic antibody versus local 4-1BB ligand gene delivery combined with interleukin-12 eradicate liver metastases of breast cancer.

    abstract::We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Martinet O,Divino CM,Zang Y,Gan Y,Mandeli J,Thung S,Pan PY,Chen SH

    更新日期:2002-06-01 00:00:00

  • Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins.

    abstract::Catheter-based percutaneous transluminal gene delivery (PTGD) into the coronary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhesion of replication...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Boekstegers P,von Degenfeld G,Giehrl W,Heinrich D,Hullin R,Kupatt C,Steinbeck G,Baretton G,Middeler G,Katus H,Franz WM

    更新日期:2000-02-01 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


    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

  • CDK4 and cyclin D1 allow human myogenic cells to recapture growth property without compromising differentiation potential.

    abstract::In vitro culture systems of human myogenic cells contribute greatly to elucidation of the molecular mechanisms underlying terminal myogenic differentiation and symptoms of neuromuscular diseases. However, human myogenic cells have limited ability to proliferate in culture. We have established an improved immortalizati...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Shiomi K,Kiyono T,Okamura K,Uezumi M,Goto Y,Yasumoto S,Shimizu S,Hashimoto N

    更新日期:2011-09-01 00:00:00

  • Efficient delivery of liposome-mediated MGMT-siRNA reinforces the cytotoxity of temozolomide in GBM-initiating cells.

    abstract::Glioblastoma multiforme (GBM) is one of the most formidable brain tumors with a mean survival period of approximately 12 months. To date, a combination of radiotherapy and chemotherapy with an oral alkylating agent, temozolomide (TMZ), has been used as first-line therapy for glioma. However, the efficacy of chemothera...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Kato T,Natsume A,Toda H,Iwamizu H,Sugita T,Hachisu R,Watanabe R,Yuki K,Motomura K,Bankiewicz K,Wakabayashi T

    更新日期:2010-11-01 00:00:00

  • Efficient gene transfer of VSV-G pseudotyped retroviral vector to human brain tumor.

    abstract::A retroviral vector constructed from the murine leukemia virus (MLV) can only express transgenes in cells undergoing mitosis, indicating its suitability as a delivery vehicle for cancer gene therapy. However, the transduction efficiency (TE) of retroviruses embedding endogenous envelope proteins in human cancer cells ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Lee H,Song JJ,Kim E,Yun CO,Choi J,Lee B,Kim J,Chang JW,Kim JH

    更新日期:2001-02-01 00:00:00

  • Insulation from viral transcriptional regulatory elements improves inducible transgene expression from adenovirus vectors in vitro and in vivo.

    abstract::Recombinant adenoviruses (Ad) are attractive vectors for gene transfer in vitro and in vivo. However, the widely used E1-deleted vectors as well as newer generation vectors contain viral sequences, including transcriptional elements for viral gene expression. These viral regulatory elements can interfere with heterolo...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Steinwaerder DS,Lieber A

    更新日期:2000-04-01 00:00:00

  • T-cell response to adenovirus hexon and DNA-binding protein in mice.

    abstract::The successful development of adenovirus vectors for vaccines and gene therapy will require a better understanding of the host immune response. Using the ELISPOT assay to measure IFN-gamma-secreting CD8(+) cells, we identify immunodominant epitopes of the adenovirus hexon and DNA-binding protein in BALB/c and C57BL/6 ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: McKelvey T,Tang A,Bett AJ,Casimiro DR,Chastain M

    更新日期:2004-05-01 00:00:00

  • Measles virus selectively blind to signaling lymphocyte activation molecule as a novel oncolytic virus for breast cancer treatment.

    abstract::Oncolytic viruses hold much promise as novel therapeutic agents that can be combined with conventional therapeutic modalities. Measles virus (MV) is known to enter cells using the signaling lymphocyte activation molecule (SLAM), which is expressed on cells of the immune system. Although human breast cancer cell lines ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Sugiyama T,Yoneda M,Kuraishi T,Hattori S,Inoue Y,Sato H,Kai C

    更新日期:2013-03-01 00:00:00

  • Ribozyme targeting of the growth factor pleiotrophin in established tumors: a gene therapy approach.

    abstract::The growth and metastasis of solid tumors relies on the activities of polypeptide growth factors to recruit stromal tissue and expand the tumor mass. Pleiotrophin (PTN) is a secreted growth factor with angiogenic activity that has been found to contribute to the growth and metastasis of tumors including melanoma. Here...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Malerczyk C,Schulte AM,Czubayko F,Bellon L,Macejak D,Riegel AT,Wellstein A

    更新日期:2005-02-01 00:00:00

  • Production and purification of lentiviral vectors generated in 293T suspension cells with baculoviral vectors.

    abstract::Lentivirus can be engineered to be a highly potent vector for gene therapy applications. However, generation of clinical grade vectors in enough quantities for therapeutic use is still troublesome and limits the preclinical and clinical experiments. As a first step to solve this unmet need we recently introduced a bac...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Lesch HP,Laitinen A,Peixoto C,Vicente T,Makkonen KE,Laitinen L,Pikkarainen JT,Samaranayake H,Alves PM,Carrondo MJ,Ylä-Herttuala S,Airenne KJ

    更新日期:2011-06-01 00:00:00

  • Gene delivery to rat and human Schwann cells and nerve segments: a comparison of AAV 1-9 and lentiviral vectors.

    abstract::Schwann cells (SCs) in an injured peripheral nerve form pathways for regenerating axons. Although these cells initially support regeneration, SCs lose their pro-regenerative properties following a prolonged period of denervation. Gene transfer to SC can enhance their therapeutic potential. In this article, we compared...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Hoyng SA,De Winter F,Gnavi S,van Egmond L,Attwell CL,Tannemaat MR,Verhaagen J,Malessy MJ

    更新日期:2015-10-01 00:00:00

  • Gene therapy progress and prospects: transcription regulatory systems.

    abstract::The clinical efficacy and safety as well as the application range of gene therapy will be broadened by developing systems capable of finely modulating the expression of therapeutic genes. Transgene regulation will be crucial for maintaining appropriate levels of a gene product within the therapeutic range, thus preven...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审


    authors: Toniatti C,Bujard H,Cortese R,Ciliberto G

    更新日期:2004-04-01 00:00:00

  • Clinical retroviral vector production: step filtration using clinically approved filters improves titers.

    abstract::Production of retroviral vectors for clinical use requires removal of cells and cellular debris. We combined a series of filters of decreasing pore size using commercially available blood banking filters approved for clinical use. The collection bag and filters can be connected to create a sterile, closed system using...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Reeves L,Cornetta K

    更新日期:2000-12-01 00:00:00

  • Prevention of autoimmune diabetes by intramuscular gene therapy with a nonviral vector encoding an interferon-gamma receptor/IgG1 fusion protein.

    abstract::We report on long-term delivery of an interferon-gamma (IFN gamma) inhibitory protein by intramuscular (i.m.) gene therapy. IFN gamma is a cytokine that plays an important role in many inflammatory disorders, including autoimmune insulin-dependent diabetes mellitus (IDDM) in NOD mice and (in various strains) multiple ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Prud'homme GJ,Chang Y

    更新日期:1999-05-01 00:00:00

  • Improved titers of HIV-based lentiviral vectors using the SRV-1 constitutive transport element.

    abstract::The development of lentiviral vectors that use Rev-independent mechanisms of nuclear export for their genomic RNA could facilitate the construction of novel anti-HIV vectors. We have improved the titers of Rev-independent lentiviral vectors having the SRV-1 CTE by mutating the major splice donor and acceptor sites pre...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Mautino MR,Keiser N,Morgan RA

    更新日期:2000-08-01 00:00:00

  • Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss.

    abstract::Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this st...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Yu H,Li Q,Herbert B,Zinna R,Martin K,Junior CR,Kirkwood KL

    更新日期:2011-04-01 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


    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

  • Efficient coexpression and secretion of anti-atherogenic human apolipoprotein AI and lecithin-cholesterol acyltransferase by cultured muscle cells using adeno-associated virus plasmid vectors.

    abstract::Plasma apolipoprotein AI (apoAI) and lecithin-cholesterol acyltransferase (LCAT) play important roles in reverse cholesterol transport, promoting the removal of excess cholesterol from peripheral cells and reducing formation of atherosclerotic lesions. Gene augmentation of either apoAI or LCAT, or both, are thus attra...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Fan L,Drew J,Dunckley MG,Owen JS,Dickson G

    更新日期:1998-10-01 00:00:00

  • Bicistronic transfer of CDKN2A and p53 culminates in collaborative killing of human lung cancer cells in vitro and in vivo.

    abstract::Cancer therapies that target a single protein or pathway may be limited by their specificity, thus missing key players that control cellular proliferation and contributing to the failure of the treatment. We propose that approaches to cancer therapy that hit multiple targets would limit the chances of escape. To this ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Xande JG,Dias AP,Tamura RE,Cruz MC,Brito B,Ferreira RA,Strauss BE,Costanzi-Strauss E

    更新日期:2020-02-01 00:00:00

  • Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.

    abstract::We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate marke...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Morsy MA,Gu MC,Zhao JZ,Holder DJ,Rogers IT,Pouch WJ,Motzel SL,Klein HJ,Gupta SK,Liang X,Tota MR,Rosenblum CI,Caskey CT

    更新日期:1998-01-01 00:00:00