Abstract:
:Malignant pleural mesothelioma (MPM) is a fatal disease with a median survival of less than 14 months. For the first time, a genetically engineered vaccinia virus is shown to produce efficient infection, replication, and oncolytic effect against MPM. GLV-1h68 is a replication-competent engineered vaccinia virus carrying transgenes encoding Renilla luciferase, green fluorescent protein (both inserted at the F14.5L locus), beta-galactosidase (inserted at the J2R locus, which encodes thymidine kinase), and beta-glucuronidase (at the A56R locus, which encodes hemagglutinin). This virus was tested in six human MPM cell lines (MSTO-211H, VAMT, JMN, H-2373, H-2452, and H-2052). GLV-1h68 successfully infected all cell lines. For the most sensitive line, MSTO-211H, expression of green fluorescent protein (GFP) started within 4 hr with increasing intensity over time until nearly 100% of cells expressed GFP at 24 hr. All cell lines were sensitive to killing by GLV-1h68, with the degree of sensitivity predictable by infectivity assay. Even the most resistant cell line exhibited 44 +/- 3.8% cell survival by day 7 when infected at a multiplicity of infection of 1.0. Viral proliferation assays demonstrated 2-to 4-fold logarithmic replication of GLV-1h68 in the cell lines tested. In an orthotopic model, GLV-1h68 effectively prevented development of cachexia and tumor-related morbidity, reduced tumor burden, and cured MPM in both early and late treatment groups. GLV-1h68 was successfully used to treat MPM in vitro and in an orthotopic model (in vivo). These promising results warrant clinical investigation of GLV-1h68 as a novel agent in the treatment of MPM.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Kelly KJ,Woo Y,Brader P,Yu Z,Riedl C,Lin SF,Chen N,Yu YA,Rusch VW,Szalay AA,Fong Ydoi
10.1089/hum.2008.036subject
Has Abstractpub_date
2008-08-01 00:00:00pages
774-82issue
8eissn
1043-0342issn
1557-7422journal_volume
19pub_type
杂志文章abstract::Gene delivery via murine-based recombinant retroviral vectors is currently widely used in gene therapy clinical trials. The vectors are engineered to be replication defective by replacing the structural and nonstructural genes of a cloned infectious retrovirus with a therapeutic gene of interest. The retroviral partic...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.10-1231
更新日期:1997-07-01 00:00:00
abstract::Virotherapy is a unique modality for the treatment of cancer with oncolytic viruses (OVs) that selectively infect and lyse tumor cells, spread within tumors, and activate anti-tumor immunity. Various viruses are being developed as OVs preclinically and clinically, several of them engineered to encode therapeutic prote...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.138
更新日期:2017-10-01 00:00:00
abstract::The use of gene-engineered T cells expressing chimeric single-chain (scFv) receptors capable of codelivering CD28 costimulation and T cell receptor zeta chain (TCR-zeta) activation signals has emerged as a promising treatment regimen for cancer. Using retroviral transduction, primary human T lymphocytes were gene-engi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/1043034041361235
更新日期:2004-07-01 00:00:00
abstract::Deficiencies in different steps of purine metabolism give rise to a number of human inherited disorders. Lesch-Nyhan syndrome is a severe neurological disorder, caused by a deficiency in the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT). HPRT-deficient mice have been generated, but have proved to...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.13-1491
更新日期:1996-08-20 00:00:00
abstract::Diabetes mellitus derives from either insulin deficiency (type I) or resistance (type II). Homozygous mutations in the insulin receptor (IR) gene cause the rare leprechaunism and Rabson-Mendenhall syndromes, severe forms of hyperinsulinemic insulin resistance for which no therapy is currently available. Systems have b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.1101
更新日期:2004-11-01 00:00:00
abstract::If established cultured cell lines genetically modified to secrete desired gene products could be implanted in different allogeneic recipients without immune rejection, novel gene products would be delivered more cost effectively. We tested this strategy by encapsulating mouse Ltk- cells transfected with the human gro...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.4-433
更新日期:1993-08-01 00:00:00
abstract::The management of disorders of the nervous system remains a medical challenge. The key goals are to understand disease mechanisms, to validate therapeutic targets, and to develop new therapeutic strategies. Viral vector-mediated gene transfer can meet these goals and vectors based on lentiviruses have particularly use...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2006.17.1
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abstract::Oncolytic measles virus (MV) encoding the human thyroidal sodium iodide symporter (MV-NIS) has proved to be safe after intraperitoneal or intravenous administration in patients with ovarian cancer or multiple myeloma, respectively, but it has not yet been administered through intratumoral injection in humans. Squamous...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.128
更新日期:2012-03-01 00:00:00
abstract::Three retroviral constructs containing a full-length human alpha-L-iduronidase (IDUA) cDNA were made. The first, pLIdSN, is designed so that expression of the IDUA cDNA is from the 5' viral long terminal repeat (LTR). The second, pLNCId, is designed to express the IDUA cDNA from the cytomegalovirus (CMV) immediate ear...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1992.3.4-371
更新日期:1992-08-01 00:00:00
abstract::Efficient and homogeneous gene transfer to cardiac myocytes is a major target in myocardial gene therapy. The aim of this study was to determine the conditions permitting efficient, homogeneous, adenovirus-mediated gene transfer to cardiac myocytes, with a view to application during coronary artery catheterization. Ge...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015329
更新日期:2000-05-01 00:00:00
abstract::Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals,...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2015.092
更新日期:2016-05-01 00:00:00
abstract::Gene transfer of reporter genes may trigger immune responses against the heterologous protein resulting in shortening of gene expression and inflammation. We generated transgenic rats expressing the lacZ gene under the control of the human immunodeficiency virus type 1 (HIV-1) long-terminal repeat (LTR) (HIV-lacZ) to ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760128603
更新日期:2002-07-20 00:00:00
abstract::Bag-1 exerts powerful antiapoptotic effects by binding and stabilizing Bcl-2 and interacting with the tumor necrosis factor receptor type I-induced death signal. We examined the effects of overexpression of Bag-1 by ex vivo adenoviral gene transfer on cold (4 degrees C for 24 hr) ischemia/reperfusion (I/R) injury of r...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340260185120
更新日期:2002-08-10 00:00:00
abstract::As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.036
更新日期:2007-12-01 00:00:00
abstract::Reporter gene-based molecular imaging can provide invaluable information on the fate of cellular therapies postimplantation. Integrating lentiviral vectors (ILVs) are commonly used for stably engineering cells; however, their potential for insertional mutagenesis poses a significant safety concern and barrier to wides...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.111
更新日期:2018-10-01 00:00:00
abstract::The efficiency of gene therapy strategies against cancer is limited by the poor distribution of the vectors in the malignant tissues. To solve this problem, a new generation of tumor-specific, conditionally replicative adenoviruses is being developed. To direct the replication of the virus to breast cancer, we have co...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050143435
更新日期:2000-09-20 00:00:00
abstract::Chronic inflammation in tibialis anterior muscles of mdx mice was produced by a single injection of a recombinant adenovirus vector (AV) expressing an immunogenic beta-galactosidase (beta-gal). In regions of intense beta-gal staining, mononuclear infiltrates abounded, and muscle fibers showed strong extrasynaptic utro...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.489
更新日期:2005-04-01 00:00:00
abstract::Previously, we described a nonviral cytoplasmic gene therapy vector system based on the T7 autogene concept. This system has been shown to achieve rapid and high levels of gene expression in a variety of animal cells and tissues. To test the utility of the system in vivo tumor ablation, a T7 cancer gene therapy plasmi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.5-729
更新日期:1998-03-20 00:00:00
abstract::Somatic gene therapy using nonautologous recombinant cells immunologically protected with alginate microcapsules has been successfully used to treat rodent genetic diseases. We now report the delivery of recombinant gene products to the brain in rodents by implanting microencapsulated cells for the purpose of eventual...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950019183
更新日期:1999-01-01 00:00:00
abstract::Previous studies have documented that the skin can be used as a bioreactor to produce proteins for systemic release to treat diseases. A gene-switch system has been developed that allows regulated expression of therapeutic genes. To determine whether this system could be used in the skin, we developed a transgenic mou...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402753812476
更新日期:2002-06-10 00:00:00
abstract::Restoration of correct splicing of βIVS2-654-globin pre-mRNA was previously accomplished in erythroid cells from β-thalassemia/HbE patients by an engineered U7 small nuclear RNA (snRNA) that carried a sequence targeted to the cryptic branch point and an exonic splicing enhancer, U7.BP+623 snRNA. In this study, this ap...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.145
更新日期:2020-11-02 00:00:00
abstract::Tumor angiogenesis is a rate-limiting factor for tumor growth, and the endothelial cells of tumor vessels display specific features that can be exploited for the selective delivery of cancer therapeutics. To specifically target exogenous genes to angiogenic tumor vessels, we generated a panel of vesicular stomatitis v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403322168028
更新日期:2003-08-10 00:00:00
abstract::Introduction of a new vaccine requires choosing a delivery system that provides safe administration and the desired level of immunogenicity. The safety, tolerability, and immunogenicity of three monthly 2.5-mg doses of a PfCSP DNA vaccine were evaluated in healthy volunteers as administered intramuscularly (IM) by nee...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340260201644
更新日期:2002-09-01 00:00:00
abstract::The clinical success of suicide gene therapy using herpes simplex virus type 1 thymidine kinase (TK) is largely dependent on the capacity of this enzyme to effectively induce the death of bystander cells. We have shown that fusion of TK to an 11-amino acid peptide from the basic domain of the human immunodeficiency vi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.1389
更新日期:2005-12-01 00:00:00
abstract::Severe fetal growth restriction (FGR) affects 1:500 pregnancies, is untreatable and causes serious neonatal morbidity and death. Reduced uterine blood flow (UBF) and lack of bioavailable VEGF due to placental insufficiency is a major cause. Transduction of uterine arteries in normal or FGR sheep and guinea pigs using ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.006
更新日期:2020-11-01 00:00:00
abstract::Bone marrow mesenchymal stem cells (BMSCs) represent an important source of cells for tissue repair. The tropism of these cells to the sites of injury and tumors has been well established. Their tumor-homing properties make BMSCs good candidates as antitumor agent delivery vehicles. In this study, we showed that BMSCs...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.116
更新日期:2011-04-01 00:00:00
abstract::Stem cell mobilization to injured tissue contributes to neovascularization, resulting in regeneration after myocardial infarction (MI). We previously showed that direct cardiac injection of a recombinant lentivirus (LV) that engineers expression of membrane-bound stem cell factor (mSCF) improves outcomes immediately a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.063
更新日期:2012-12-01 00:00:00
abstract::Adoptive cellular therapy has evolved into a powerful force in the battle against cancer, holding promise for curative responses in patients with advanced and refractory tumors. Autologous T cells, reprogrammed to target malignant cells via the expression of a chimeric antigen receptor (CAR) represent the frontrunner ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.236
更新日期:2018-05-01 00:00:00
abstract::Recombinant adeno-associated virus serotype 2 (rAAV2)-based human gene therapy for cystic fibrosis has progressed through a series of preclinical studies and phase I and II clinical trials. This agent has shown an encouraging safety profile, consistent levels of DNA transfer, and positive evidence of short-term clinic...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
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更新日期:2005-08-01 00:00:00
abstract::Retinal ganglion cells (RGCs) play a key role in the pathogenesis and development of glaucoma. The present study aims to investigate the underlying mechanism of long noncoding RNA growth arrest-specific transcript 5 (GAS5) in glaucoma development through regulating the apoptosis of RGCs. Rat models of chronic glaucoma...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.056
更新日期:2019-12-01 00:00:00