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


: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 T cells, is known to amplify T cell-mediated immunity. In this study, we compared the effect of a systemically delivered agonistic anti-4-1BB monoclonal antibody (anti-4-1BB mAb) with intra-tumoral adenoviral-mediated gene transfer of the 4-1BB ligand (ADV/4-1BBL) to liver metastases in a syngeneic animal model of breast cancer. Both treatments induced a dramatic regression of pre-established tumor. When combined with intra-tumoral delivery of the IL-12 gene, both anti-4-1BB mAb and ADV/4-1BBL were synergistic and led to survival rates of 87% and 78%, respectively. The anti-tumor immunity is mainly mediated by CD4+ T cells in IL-12 plus 4-1BB ligand-treated animals, and CD8+ T cells in IL-12 plus anti-4-1BB mAb-treated animals. However, only long-term survivors after treatment with IL-12 and 4-1BBL genes have showed significantly potent, systemic, and tumor-specific T cell-mediated immunity.


Gene Ther


Gene therapy


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





Has Abstract


2002-06-01 00:00:00












  • Why commercialization of gene therapy stalled; examining the life cycles of gene therapy technologies.

    abstract::This report examines the commercialization of gene therapy in the context of innovation theories that posit a relationship between the maturation of a technology through its life cycle and prospects for successful product development. We show that the field of gene therapy has matured steadily since the 1980s, with th...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Ledley FD,McNamee LM,Uzdil V,Morgan IW

    更新日期:2014-02-01 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


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

    更新日期:2007-06-01 00:00:00

  • Controlled propagation of replication-competent Sindbis viral vector using suicide gene strategy.

    abstract::A major concern of using viral gene therapy is the potential for uncontrolled vector propagation and infection that might result in serious deleterious effects. To enhance the safety, several viral vectors, including vectors based on Sindbis virus, were engineered to lose their capability to replicate and spread after...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Tseng JC,Daniels G,Meruelo D

    更新日期:2009-02-01 00:00:00

  • Overexpression of arylsulfatase A gene in fibroblasts from metachromatic leukodystrophy patients does not induce a new phenotype.

    abstract::We tested the influence of overexpression of arylsulfatase A (ASA) on the activity of other sulfatases in fibroblasts from patients with metachromatic leukodystrophy (MLD). We demonstrated that the overexpression of ASA reduces the activity of various sulfatases by a small amount but does not induce an accumulation of...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Ohashi T,Matalon R,Barranger JA,Eto Y

    更新日期:1995-08-01 00:00:00

  • Enhanced transduction efficiency of retroviral vectors coprecipitated with calcium phosphate.

    abstract::Retroviral vectors are being used increasingly in clinical gene therapy protocols but low transduction frequencies are presenting a significant obstacle to progress. In this paper we report a simple method to enhance the efficiency of ex vivo retroviral gene transfer. Calcium chloride is added to the vector stock and ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Morling FJ,Russell SJ

    更新日期:1995-09-01 00:00:00

  • Cultured human myoblasts and myotubes show markedly different transducibility by replication-defective adenovirus recombinants.

    abstract::Human adenovirus (AV) is a favored vector for delivery of therapeutic genes into certain target cells, such as skeletal muscle cells for gene therapy. Here we show that replication-defective (E1 + E3 deleted) human type 5 adenovirus (AV) recombinants containing a reporter gene insert (RSV-luciferase or RSV-Lux) can ve...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Acsadi G,Jani A,Huard J,Blaschuk K,Massie B,Holland P,Lochmüller H,Karpati G

    更新日期:1994-09-01 00:00:00

  • Harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus.

    abstract::The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of in...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Zhen S,Hua L,Liu YH,Gao LC,Fu J,Wan DY,Dong LH,Song HF,Gao X

    更新日期:2015-05-01 00:00:00

  • Utility of Epstein-Barr virus-encoded small RNA promoters for driving the expression of fusion transcripts harboring short hairpin RNAs.

    abstract::To induce RNA interference (RNAi), either small interfering RNAs (siRNAs) are directly introduced into the cell or short hairpin RNAs (shRNAs) are expressed from a DNA vector. At present, shRNAs are commonly synthesized by RNA polymerase III (Pol III) promoters of the H1 and U6 RNAs. In this study, we designed and cha...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Choy EY,Kok KH,Tsao SW,Jin DY

    更新日期:2008-02-01 00:00:00

  • Continuous secretion of human soluble CD4 in mice transplanted with genetically modified cells.

    abstract::Somatic transgenesis can be used to confer endogenous production of proteins with therapeutic properties. One such product, recombinant soluble human CD4 (sCD4), has been shown to be an efficient inhibitor of human immunodeficiency virus 1 (HIV-1) in vitro, but its too short half-life in vivo has impaired long-term cl...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Valere T,Bohl D,Klatzmann D,Danos O,Sonigo P,Heard JM

    更新日期:1995-05-01 00:00:00

  • Sustained inhibition of hepatitis B virus replication in vivo using RNAi-activating lentiviruses.

    abstract::Chronic infection with hepatitis B virus (HBV) puts individuals at high risk for complicating cirrhosis and liver cancer, but available treatment to counter the virus rarely eliminates infection. Although harnessing RNA interference (RNAi) to silence HBV genes has shown the potential, achieving efficient and durable s...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Ivacik D,Ely A,Ferry N,Arbuthnot P

    更新日期:2015-02-01 00:00:00

  • Herpesvirus microRNAs for use in gene therapy immune-evasion strategies.

    abstract::Transplantation of allogeneic cells as well as of genetically corrected autologous cells are potent approaches to restore cellular functions in patients suffering from genetic diseases. The recipient's immune responses against non-self-antigens may compromise the survival of the grafted cells. Recipients of the graft ...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审


    authors: Bots STF,Hoeben RC

    更新日期:2017-07-01 00:00:00

  • Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy.

    abstract::The sodium iodide symporter (NIS) mediates iodide uptake into thyrocytes and is the molecular basis of thyroid radioiodine therapy. We previously have shown that NIS gene transfer into the F98 rat gliomas facilitated tumor imaging and increased survival by radioiodine. In this study, we show that: (1) the therapeutic ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Shen DH,Marsee DK,Schaap J,Yang W,Cho JY,Hinkle G,Nagaraja HN,Kloos RT,Barth RF,Jhiang SM

    更新日期:2004-01-01 00:00:00

  • Demyelination but no cognitive, motor or behavioral deficits after adenovirus-mediated gene transfer into the brain.

    abstract::Adenovirus-mediated gene transfer of interferon gamma (AdIFN) elicits rejection of intracerebral Lewis lung carcinoma. In this system, gene transfer into brain parenchymal cells is both necessary and sufficient to generate the antitumor response. Despite persistent parenchymal inflammation and demyelination, wild-type...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Fathallah-Shaykh HM,Kafrouni AI,Zhao LJ,Diaz-Arrastia R,Garcia JA,Frawley WH,Forman J

    更新日期:2000-12-01 00:00:00

  • PML has a predictive role in tumor cell permissiveness to interferon-sensitive oncolytic viruses.

    abstract::The oncotropic phenotypes of several viruses correlate with tumor-associated deficiencies within interferon (IFN) signaling pathways. This observation formed the conceptual basis for developing oncolytic viruses deleted for viral proteins that inhibit the host IFN-dependent antiviral response, such as herpes simplex v...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Sobol PT,Hummel JL,Rodrigues RM,Mossman KL

    更新日期:2009-09-01 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

  • Kinetics and characteristics of replication-competent revertants derived from self-inactivating foamy virus vectors.

    abstract::In this study, self-inactivating (SIN) retroviral vectors based on feline foamy virus (FFV) were constructed and analysed. The FFV SIN vectors were devoid of the core FFV long terminal repeat promoter plus upstream sequences but contained all structural and regulatory genes. This design allowed sensitive detection of ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Bastone P,Löchelt M

    更新日期:2004-03-01 00:00:00

  • In vivo suppression of restenosis in balloon-injured rat carotid artery by adenovirus-mediated gene transfer of the cell surface-directed plasmin inhibitor ATF.BPTI.

    abstract::Injury-induced neointimal development results from migration and proliferation of vascular smooth muscle cells (SMC). Cell migration requires controlled proteolytic degradation of extracellular matrix surrounding the cell. Plasmin is a major contributor to this process by degrading various matrix proteins directly, or...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Lamfers ML,Lardenoye JH,de Vries MR,Aalders MC,Engelse MA,Grimbergen JM,van Hinsbergh VW,Quax PH

    更新日期:2001-04-01 00:00:00

  • Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys.

    abstract::In-stent restenosis results exclusively from neointimal hyperplasia due to mechanical injury and a foreign body response to the prosthesis. Inflammation mediated by monocyte chemoattractant protein-1 (MCP-1) might therefore underlie in-stent restenosis. We recently devised a new strategy for anti-MCP-1 gene therapy by...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Ohtani K,Usui M,Nakano K,Kohjimoto Y,Kitajima S,Hirouchi Y,Li XH,Kitamoto S,Takeshita A,Egashira K

    更新日期:2004-08-01 00:00:00

  • Bystander effect of purine nucleoside analogues in HSV-1 tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues.

    abstract::Introduction of the herpes simplex virus type 1 thymidine kinase gene into tumor cells, followed by the administration of the antiherpes nucleoside analogue ganciclovir has been demonstrated to be effective in eliminating solid tumors in animals. The success of this combination treatment largely depends on the bystand...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Degrève B,De Clercq E,Balzarini J

    更新日期:1999-02-01 00:00:00

  • Human urinary bladder carcinomas express adenovirus attachment and internalization receptors.

    abstract::The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)bet...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Loskog A,Hedlund T,Wester K,de la Torre M,Philipson L,Malmström PU,Tötterman TH

    更新日期:2002-05-01 00:00:00

  • Doxycycline-regulated lentiviral vector system with a novel reverse transactivator rtTA2S-M2 shows a tight control of gene expression in vitro and in vivo.

    abstract::Regulated expression of therapeutic genes is required for long-term gene therapy applications for many disorders. Here we describe a doxycycline (dox)-regulated lentiviral vector system consisting of two HIV-1-based self-inactivating viruses. One of the vectors is constitutively expressing a novel improved version of ...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Koponen JK,Kankkonen H,Kannasto J,Wirth T,Hillen W,Bujard H,Ylä-Herttuala S

    更新日期:2003-03-01 00:00:00

  • Adenovirus vectors for gene transduction into mobilized blood CD34+ cells.

    abstract::Mobilized blood CD34+ cells from cancer patients were ex vivo infected by a recombinant adenovirus vector carrying an alkaline phosphatase gene, whose expression is evaluable by flow cytometry. A mean of 40% CD34+ cells were infected by the vector, with high levels of expression of the transgene. Among attempts to imp...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Bregni M,Shammah S,Malaffo F,Di Nicola M,Milanesi M,Magni M,Matteucci P,Ravagnani F,Jordan CT,Siena S,Gianni AM

    更新日期:1998-04-01 00:00:00

  • Towards hematopoietic stem cell-mediated protection against infection with human immunodeficiency virus.

    abstract::The failure of pharmacological approaches to cure infection with the human immunodeficiency virus (HIV) has renewed the interest in gene-based therapies. Among the various strategies that are currently explored, the blockade of HIV entry into susceptible T cells and macrophages promises to be the most powerful interve...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Schambach A,Schiedlmeier B,Kühlcke K,Verstegen M,Margison GP,Li Z,Kamino K,Bohne J,Alexandrov A,Hermann FG,von Laer D,Baum C

    更新日期:2006-07-01 00:00:00

  • Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus.

    abstract::The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this re...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Barr E,Carroll J,Kalynych AM,Tripathy SK,Kozarsky K,Wilson JM,Leiden JM

    更新日期:1994-01-01 00:00:00

  • Imaging and tissue biodistribution of 99mTc-labeled adenovirus knob (serotype 5).

    abstract::Hepatic sequestration of systemically administered adenoviral vectors reduces the number of viral particles available for delivery to other tissues. The biological basis of this phenomenon was investigated using a new in vivo technique which permitted imaging in real time. Recombinant adenovirus serotype 5 knob (Ad5K)...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Zinn KR,Douglas JT,Smyth CA,Liu HG,Wu Q,Krasnykh VN,Mountz JD,Curiel DT,Mountz JM

    更新日期:1998-06-01 00:00:00

  • 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


    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

  • Role of antigen-specific regulatory CD4+CD25+ T cells in tolerance induction after neonatal IP administration of AAV-hF.IX.

    abstract::Neonatal AAV8-mediated Factor IX (F.IX) gene delivery was applied as a model for exploring mechanisms of tolerance induction during immune ontogeny. Intraperitoneal delivery of AAV8/ Factor IX (hF.IX) during weeks 1-4 of life, over a 20-fold dose range, directed stable hF.IX expression, correction of coagulopathy in F...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Shi Y,Falahati R,Zhang J,Flebbe-Rehwaldt L,Gaensler KM

    更新日期:2013-10-01 00:00:00

  • Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium.

    abstract::Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for t...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Connor RJ,Engler H,Machemer T,Philopena JM,Horn MT,Sutjipto S,Maneval DC,Youngster S,Chan TM,Bausch J,McAuliffe JP,Hindsgaul O,Nagabhushan TL

    更新日期:2001-01-01 00:00:00

  • Retrovirus-mediated gene transfer in lungs of living fetal sheep.

    abstract::In utero somatic gene transfer may be a useful therapeutic strategy for a variety of inherited disorders. In the present study, we demonstrate transgene expression in the airways of fetal lamb lungs, 2-3 weeks after injection of Moloney murine leukemia retrovirus based vectors containing cDNA for beta-galactosidase (l...

    journal_title:Gene therapy

    pub_type: 杂志文章


    authors: Pitt BR,Schwarz MA,Pilewski JM,Nakayama D,Mueller GM,Robbins PD,Watkins SA,Albertine KH,Bland RD

    更新日期:1995-07-01 00:00:00

  • Gene therapy progress and prospects--vectorology: design and production of expression cassettes in AAV vectors.

    abstract::Adeno-associated virus (AAV) derived vectors are considered highly eligible vehicles for human gene therapy. Not only do they possess many great potential for clinical applications due to their wide range of tissue targets but also their excellent preclinical safety profile makes them particularly suitable candidates ...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审


    authors: Le Bec C,Douar AM

    更新日期:2006-05-01 00:00:00