Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: a phase I trial.

Abstract:

:Both replication-incompetent and replication-selective adenoviruses are being developed for the treatment of cancer and other diseases. Concerns have been raised about the safety of intra-vascular adenovirus administration following a patient death on a clinical trial with a replication-defective adenovirus. In addition, the feasibility of vascular delivery to distant tumors has been questioned. dl1520 (ONYX-015) is a replication-selective adenovirus that has previously shown safety and antitumoral activity following intratumoral injection. This is the first report of intra-vascular administration with a genetically engineered, replication-selective virus. A phase I dose-escalation trial was performed in patients with liver-predominant gastrointestinal carcinoma (n = 11 total; primarily colorectal). dl1520 was infused into the hepatic artery at doses of 2 x 10(8)-2 x 10(1)2 particles for two cycles (days 1 and 8). Subsequent cycles of dl1520 were administered in combination with intravenous 5-fluorouracil (5-FU) and leucovorin. No dose-limiting toxicity, maximally tolerated dose or treatment-emergent clinical hepatotoxicity were identified following dl1520 infusion. Mild to moderate fever, rigors and fatigue were the most common adverse events. Antibody titers increased significantly in all patients. Viral replication was detectable in patients receiving the highest two doses. An objective response was demonstrated in combination with chemotherapy in a patient who was refractory to both 5-FU and dl1520 as single agents. Therefore, hepatic artery infusion of the attenuated adenovirus dl1520 was well-tolerated at doses resulting in infection, replication and chemotherapy-associated antitumoral activity.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Reid T,Galanis E,Abbruzzese J,Sze D,Andrews J,Romel L,Hatfield M,Rubin J,Kirn D

doi

10.1038/sj.gt.3301512

keywords:

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

1618-26

issue

21

eissn

0969-7128

issn

1476-5462

journal_volume

8

pub_type

临床试验,杂志文章
  • 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

  • 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

    doi:10.1038/sj.gt.3302185

    authors: Bastone P,Löchelt M

    更新日期:2004-03-01 00:00:00

  • Use of transcriptional regulatory elements of the MUC1 and ERBB2 genes to drive tumour-selective expression of a prodrug activating enzyme.

    abstract::In order to exploit differences in gene expression between normal and malignant cells for genetic prodrug-activation therapy, we have generated recombinant retroviruses containing the herpes simplex virus thymidine kinase coding region cloned downstream of sequences derived from the 5'-flanking regions of the MUC1 and...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3300510

    authors: Ring CJ,Blouin P,Martin LA,Hurst HC,Lemoine NR

    更新日期:1997-10-01 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

    doi:10.1038/sj.gt.3302147

    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

  • Gene therapy progress and prospects: stem cell plasticity.

    abstract::With the identification of stem cell plasticity several years ago, multiple reports raised hopes that tissue repair by stem cell transplantation could be within reach in the near future. Krause et al reported that a single purified hematopoietic stem cell not only repopulated the bone marrow of a host animal, but also...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3302571

    authors: Kashofer K,Bonnet D

    更新日期:2005-08-01 00:00:00

  • Intravenous injection of oligodeoxynucleotides to the NF-kappaB binding site inhibits hepatic metastasis of M5076 reticulosarcoma in mice.

    abstract::We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation in vivo. In the present study, we employed decoy ODN targeting the transcription factor nu...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301478

    authors: Kawamura I,Morishita R,Tsujimoto S,Manda T,Tomoi M,Tomita N,Goto T,Ogihara T,Kaneda Y

    更新日期:2001-06-01 00:00:00

  • Effect of decorin on overcoming the extracellular matrix barrier for oncolytic virotherapy.

    abstract::The pressing challenge for contemporary gene therapy is to deliver enough therapeutic genes to enough cancer cells in vivo. With the aim of improving viral distribution and tumor penetration, we explored the use of decorin to enhance viral spreading and tumor tissue penetration. We generated decorin-expressing replica...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.142

    authors: Choi IK,Lee YS,Yoo JY,Yoon AR,Kim H,Kim DS,Seidler DG,Kim JH,Yun CO

    更新日期:2010-02-01 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

    doi:10.1038/sj.gt.3302465

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

    更新日期:2005-04-01 00:00:00

  • Evaluation in vitro and in vivo of cationic liposome-expression construct complexes for cystic fibrosis gene therapy.

    abstract::We have tested the cationic liposome N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethyl-ammoniummethylsul phate, (DOTAP), for gene delivery in vitro and in vivo with a view to clinical use in gene therapy for cystic fibrosis. Delivery of lacZ cDNA-DOTAP complexes via aerosol showed promoter-dependent differences in the pat...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: McLachlan G,Davidson DJ,Stevenson BJ,Dickinson P,Davidson-Smith H,Dorin JR,Porteous DJ

    更新日期:1995-11-01 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

    doi:10.1038/sj.gt.3301139

    authors: Steinwaerder DS,Lieber A

    更新日期:2000-04-01 00:00:00

  • Amelioration of antigen-induced arthritis in rats by transfer of extracellular superoxide dismutase and catalase genes.

    abstract::Reactive oxygen species (ROS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), while antioxidant enzymes, such as extracellular superoxide dismutase (EC-SOD) and catalase, block radical-induced events. The present study tested if the ex vivo transfer of EC-SOD and catalase genes alone or in combi...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301916

    authors: Dai L,Claxson A,Marklund SL,Feakins R,Yousaf N,Chernajovsky Y,Winyard PG

    更新日期:2003-04-01 00:00:00

  • Apical barriers to airway epithelial cell gene transfer with amphotropic retroviral vectors.

    abstract::Gene transfer to airway epithelia with amphotropic pseudotyped retroviral vectors is inefficient following apical vector application. To better understand this inefficiency, we localized the expression of Pit2, the amphotropic receptor, in polarized human airway epithelia. Pit2 was expressed on both the apical and bas...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301714

    authors: Wang G,Williams G,Xia H,Hickey M,Shao J,Davidson BL,McCray PB

    更新日期:2002-07-01 00:00:00

  • Pharmacokinetic and pharmacodynamic study of intratumoral injection of an adenovirus encoding endostatin in patients with advanced tumors.

    abstract::Angiogenesis plays a pivotal role in tumor growth, tissue invasion and metastasis. Endostatin is an angiogenesis inhibitor and has been shown to reduce tumor growth in animal models. However, therapy with recombinant endostatin protein was hampered by its short half-life and very-low yield of bioactive protein. We per...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3303038

    authors: Li HL,Li S,Shao JY,Lin XB,Cao Y,Jiang WQ,Liu RY,Zhao P,Zhu XF,Zeng MS,Guan ZZ,Huang W

    更新日期:2008-02-01 00:00:00

  • HSV1 vectors to study protein targeting in neurones: are glycosyl-phosphatidylinositol anchors polarized targeting signals in neurones?

    abstract::In order to characterize protein targeting signals in polarized postmitotic cortical neurones in vitro, we have developed recombinant and amplicon type vectors derived from herpes simplex virus 1 (HSV1) to transfer genes into these cells. We examined the targeting of both bacterial proteins, which lack specific target...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:

    authors: Lowenstein PR,Bain D,Morrison EE,Preston CM,Clissold P,Fournel S,Epstein A,Castro MG

    更新日期:1994-01-01 00:00:00

  • Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces cell cycle arrest and apoptosis in colorectal cancer cell lines: potential application to gene therapy of colorectal cancer.

    abstract::p53 gene therapy is being tested clinically for the treatment of human cancer, however, some cancer models (in vivo and in vitro) are resistant to p53. To explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via a...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301538

    authors: Sasaki Y,Morimoto I,Ishida S,Yamashita T,Imai K,Tokino T

    更新日期:2001-09-01 00:00:00

  • Isolated limb perfusion: a novel delivery system for wild-type p53 and fiber-modified oncolytic adenoviruses to extremity sarcoma.

    abstract::Isolated limb perfusion (ILP) is a limb salvage surgical modality used to deliver chemotherapy and biologic agents to locally advanced and recurrent extremity soft tissue sarcoma (STS), and may be readily tailored for delivery of gene therapy. We set out to test the feasibility of delivering AdFLAGp53 (replication inc...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302911

    authors: Hannay J,Davis JJ,Yu D,Liu J,Fang B,Pollock RE,Lev D

    更新日期:2007-04-01 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

    doi:10.1038/sj.gt.3302846

    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

  • Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals.

    abstract::Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF), and at a molecular level reduced expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) is a major contributor. Previous studies in small animals have suggested that restoration of SERCA function is benef...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2008.120

    authors: Byrne MJ,Power JM,Preovolos A,Mariani JA,Hajjar RJ,Kaye DM

    更新日期:2008-12-01 00:00:00

  • Muscle-derived stem cells.

    abstract::The existence of cells with stem cell-like abilities derived from various tissues can now be extended to include the skeletal muscle compartment. Although researchers have focused on the utilization of these cells with regard to their myogenic capacity, initially exploring more efficient cellular therapy treatments fo...

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/sj.gt.3301719

    authors: Jankowski RJ,Deasy BM,Huard J

    更新日期:2002-05-01 00:00:00

  • Gene doping detection: evaluation of approach for direct detection of gene transfer using erythropoietin as a model system.

    abstract::As clinical gene therapy has progressed toward realizing its potential, concern over misuse of the technology to enhance performance in athletes is growing. Although 'gene doping' is banned by the World Anti-Doping Agency, its detection remains a major challenge. In this study, we developed a methodology for direct de...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2010.49

    authors: Baoutina A,Coldham T,Bains GS,Emslie KR

    更新日期:2010-08-01 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

  • Minimal ureagenesis is necessary for survival in the murine model of hyperargininemia treated by AAV-based gene therapy.

    abstract::Hyperammonemia is less severe in arginase 1 deficiency compared with other urea cycle defects. Affected patients manifest hyperargininemia and infrequent episodes of hyperammonemia. Patients typically suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation, s...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2014.106

    authors: Hu C,Tai DS,Park H,Cantero G,Cantero-Nieto G,Chan E,Yudkoff M,Cederbaum SD,Lipshutz GS

    更新日期:2015-02-01 00:00:00

  • Locoregional intravascular viral therapy of cancer: precision guidance for Paris's arrow?

    abstract::Viral therapy of cancer includes strategies such as viral transduction of tumour cells with 'suicide genes', using viral infection to trigger immune-mediated tumour cell death and using oncolytic viruses for their direct anti-tumour action. However, problems still remain in terms of adequate viral delivery to tumours....

    journal_title:Gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/gt.2010.48

    authors: Pencavel T,Seth R,Hayes A,Melcher A,Pandha H,Vile R,Harrington KJ

    更新日期:2010-08-01 00:00:00

  • Retroviral vector integration in post-transplant hematopoiesis in mice conditioned with either submyeloablative or ablative irradiation.

    abstract::X-linked chronic granulomatous disease (X-CGD) is an inherited immunodeficiency with absent phagocyte NADPH-oxidase activity caused by defects in the gene-encoding gp91(phox). Here, we evaluated strategies for less intensive conditioning for gene therapy of genetic blood disorders without selective advantage for gene ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.96

    authors: Sadat MA,Dirscherl S,Sastry L,Dantzer J,Pech N,Griffin S,Hawkins T,Zhao Y,Barese CN,Cross S,Orazi A,An C,Goebel WS,Yoder MC,Li X,Grez M,Cornetta K,Mooney SD,Dinauer MC

    更新日期:2009-12-01 00:00:00

  • Tumor-specific therapeutic effect induced by an oncolytic adenoviral vector containing heat shock protein 70 and prodrug activation genes.

    abstract::We constructed a melanoma-specific oncolytic adenoviral vector Ad.MCDIRESE1.71Hsp3, in which the cytosine deaminase and adenoviral E1A genes linked by the IRES sequence were under the control of a mouse tyrosinase enhancer/promoter transcriptional element in the E1 region of the vector. We also inserted the human heat...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302776

    authors: Liu Y,Ye T,Sun D,Maynard J,Deisseroth A

    更新日期:2006-08-01 00:00:00

  • Species differences in transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the size of endothelial fenestrae.

    abstract::Sinusoidal fenestrae may restrict the transport of gene transfer vectors according to their size. Using Vitrobot technology and cryo-electron microscopy, we show that the diameter of human adenoviral serotype 5 vectors is 93 nm with protruding fibers of 30 nm. Thus, a diameter of fenestrae of 150 nm or more is likely ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302899

    authors: Snoeys J,Lievens J,Wisse E,Jacobs F,Duimel H,Collen D,Frederik P,De Geest B

    更新日期:2007-04-01 00:00:00

  • Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer model.

    abstract::We have previously synthesized a new cationic liposome that displays high efficiency and low toxicity, 3 beta[l-ornithinamide-carbamoyl] cholesterol (O-Chol), using solid-phase synthesis. In this study, O-Chol was applied to in vitro and in vivo models of ovarian cancer. Intraperitoneal gene delivery for peritoneal di...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301704

    authors: Lee MJ,Cho SS,You JR,Lee Y,Kang BD,Choi JS,Park JW,Suh YL,Kim JA,Kim DK,Park JS

    更新日期:2002-07-01 00:00:00

  • Foamy virus--adenovirus hybrid vectors.

    abstract::To confer adenovirus vectors (AdV), the feature of integration into the host cell genome hybrid vectors were characterized in vitro, which express vectors derived from the prototypic foamy virus (FV) in the backbone of a high-capacity AdV. FVs constitute a subfamily of retroviruses with a distinct replication pathway ...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3302216

    authors: Picard-Maureau M,Kreppel F,Lindemann D,Juretzek T,Herchenröder O,Rethwilm A,Kochanek S,Heinkelein M

    更新日期:2004-04-01 00:00:00

  • Poly-L-glutamate, an anionic polymer, enhances transgene expression for plasmids delivered by intramuscular injection with in vivo electroporation.

    abstract::Intramuscular (i.m.) injection of plasmids followed by electropermeabilization is an efficient process to deliver genes into skeletal myofibers that permits proteins to be produced and secreted at therapeutically relevant levels. To further improve skeletal muscle as a bioreactor, we identified a formulation that elev...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.gt.3301806

    authors: Nicol F,Wong M,MacLaughlin FC,Perrard J,Wilson E,Nordstrom JL,Smith LC

    更新日期:2002-10-01 00:00:00

  • PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.

    abstract::Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of P...

    journal_title:Gene therapy

    pub_type: 杂志文章

    doi:10.1038/gt.2009.117

    authors: Chang PC,Seol YJ,Cirelli JA,Pellegrini G,Jin Q,Franco LM,Goldstein SA,Chandler LA,Sosnowski B,Giannobile WV

    更新日期:2010-01-01 00:00:00