Abstract:
:Mice bearing breast tumors were treated with a single dose of an adenovirus expressing interleukin-12 (AdmIL-12.1) injected intratumorally, which produced regressions in greater than 75% of the treated tumors; approximately one-third of the animals remained tumor free. Complete regression was associated with immunity to secondary challenge with fresh tumor cells. Analysis of local cytokine expression demonstrated maximum expression of IL-12 within the tumor between 24 and 72 hr post-injection, reaching 600-800 ng per tumor, with elevated local levels of IL-12 detectable for at least 9 days. This expression was highly localized as serum IL-12 peaked at 40-60 ng/ml at 24 hr and was less than 10 ng/ml from day 3 onward. Interferon-gamma (IFN-gamma) concentrations were markedly increased within the tumor following AdmIL-12.1 administration, demonstrating that IL-12 was acting locally. Tumor-draining lymph node cells spontaneously produced IFN-gamma following AdmIL-12.1 treatment, suggesting these cells were activated by IL-12. These data demonstrate that AdmIL-12.1 can be used to deliver very high levels of localized cytokine production. Moreover, we have confirmed that the IL-12 produced from our vector actually affects the local cytokine environment of the tumor and activates responder cells present within the tumor.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Bramson JL,Hitt M,Addison CL,Muller WJ,Gauldie J,Graham FLdoi
10.1089/hum.1996.7.16-1995subject
Has Abstractpub_date
1996-10-20 00:00:00pages
1995-2002issue
16eissn
1043-0342issn
1557-7422journal_volume
7pub_type
杂志文章abstract::Janus kinase 3 (JAK3) is an essential component of cytokine receptor signal transduction pathways required for normal lymphocyte development and function. JAK3 deficiency in both mice and humans results in severe combined immunodeficiency (SCID) and increased susceptibility to opportunistic infections. We have previou...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303400750038462
更新日期:2000-11-20 00:00:00
abstract::The field of adenovirology is undergoing rapid change in response to increasing appreciation of the potential advantages of adenoviruses as the basis for new vaccines and as vectors for gene and cancer therapy. Substantial knowledge and understanding of adenoviruses at a molecular level has made their manipulation for...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2013.235
更新日期:2014-04-01 00:00:00
abstract::We reported total correction of blood coagulation plasma factor VIII (FVIII) activity, using adeno-associated virus serotype 8 (AAV8) vectors for liver-specific gene transfer in hemophilia A mice. We now show, irrespective of immunosuppression or route of administration, total long-term correction of hemophilia A mice...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.427
更新日期:2006-04-01 00:00:00
abstract::Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the development of cellular immunity. Clinical applications for this lymphokine include resolution of infectious disease, cancer immunotherapy, and boosting cellular immunity in AIDS patients. When using IL-12 and other cytokines therap...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.3-333
更新日期:1996-02-10 00:00:00
abstract::The use of nonionic polymeric micelles orally to protect and deliver plasmid DNA in vivo was investigated. Parathyroid hormone (PTH)(1-34) gene (179 bp) was inserted into a human cytomegalovirus promoter (PCMV) and E. coli competent cells were used to amplify the cDNA. Polymeric micelle formations (100 microl) formed ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.015
更新日期:2009-11-01 00:00:00
abstract::Retroviral vectors encoding glucose-responsive promoters driving furin expression may provide an amplified, glucose-regulated secretion of insulin. We constructed LhI*TFSN virus to encode a glucose-regulatable transforming growth factor alpha promoter controlling furin expression with a viral LTR promoter driving cons...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750061195
更新日期:2001-01-20 00:00:00
abstract::The liver is an attractive target tissue for gene therapy. Current approaches for hepatic gene delivery include retroviral and adenoviral vectors, liposome/DNA, and peptide/DNA complexes. This study describes a technique for direct injection of DNA into liver that led to significant gene expression. Gene expression wa...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1994.5.12-1477
更新日期:1994-12-01 00:00:00
abstract::Although recombinant adeno-associated virus serotype 8 (AAV8) and serotype 5 (AAV5) vectors have shown efficacy in Phase 1 clinical trials for gene therapy of hemophilia B, it has become increasingly clear that these serotypes are not optimal for transducing primary human hepatocytes. We have previously reported that ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.099
更新日期:2020-10-01 00:00:00
abstract::This Phase I study, "Ribozyme Gene Therapy of HIV-1 Infection" (UCSD HSC #971072, FDA BB-IND 6405), is a prospective, open-label trial of infusion of autologous gene-altered cells into asymptomatic HIV-1 seropositive individuals. The objectives of this trial are to test the safety, feasibility, and potential efficacy ...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.1998.9.16-2407
更新日期:1998-11-01 00:00:00
abstract::Three-vessel disease (TVD) is a severe coronary heart disease (CHD) with poor prognosis. Niemann-Pick C1-like 1 (NPC1L1) is a transporter protein for exogenous cholesterol absorption, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is a rate-limiting enzyme for cholesterol synthesis. We aimed to investigat...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.229
更新日期:2021-01-22 00:00:00
abstract::Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34(+) cells from CB at weeks 24 to 34 of pregnan...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340150504000
更新日期:2001-03-01 00:00:00
abstract::Cell encapsulation offers a safe and manufacturable method for the systemic delivery of therapeutic proteins from genetically engineered cells. However, control of dose delivery remains a major issue with regard to clinical application. We generated populations of immortalized murine NIH 3T3 fibroblasts that secrete m...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950018823
更新日期:1999-02-10 00:00:00
abstract::For the successful application of RNA interference in vivo, it is desired to achieve (local) delivery of small interfering RNAs (siRNAs) and long-term gene silencing. Nonviral electrodelivery is suitable to obtain local and prolonged expression of transgenes. By intramuscular electrodelivery of a plasmid in which two ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.176
更新日期:2007-09-01 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::Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronar...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1089/10430340050016003
更新日期:2000-01-20 00:00:00
abstract::Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) offer great hope for in vitro modeling of Parkinson's disease (PD), as well as for designing cell-replacement therapies. To realize these opportunities, there is an urgent need to develop efficient protocols for the directed differentiation of...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.054
更新日期:2012-01-01 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::Recombinant vectors based on adeno-associated virus serotype 8 (AAV8) have been successfully used in the clinic and hold great promise for liver-directed gene therapy. Preexisting immunity against AAV8 or the development of antibodies against the therapeutic transgene product might negatively affect the outcomes of ge...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2014.109
更新日期:2015-03-01 00:00:00
abstract::Doxycycline (DOX) is widely used as a pharmacological agent and as an effector molecule in inducible gene expression systems. For most applications, it is important to determine whether the DOX concentration reaches the level required for optimal efficacy. We developed a sensitive bioassay for measuring the DOX concen...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.182
更新日期:2009-05-01 00:00:00
abstract::Malignant mesothelioma is a tumor of the pleura for which there is no satisfactory treatment. It is almost universally fatal, regardless of the stage of the tumor at the time of diagnosis. Current treatment modalities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalitie...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.1998.9.17-2641
更新日期:1998-11-20 00:00:00
abstract::This study focuses on the design, construction, and evaluation of a chimeric promoter for gene therapy applications where it is desirable to have low-level basal expression of the newly transferred gene, which can be induced to higher levels of expression by the administration of pharmacologic agents that can be safel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.15-1883
更新日期:1996-10-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) and other inherited myopathies lead to progressive destruction of most skeletal muscles in the body, including those responsible for maintaining respiration. DMD is a fatal disorder caused by defects in the dystrophin gene. Recombinant adenovirus vectors (AdV) are considered a promisi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015608
更新日期:2000-03-20 00:00:00
abstract::Somatic gene therapy for pulmonary diseases must be accomplished in vivo, requiring the spread of a gene transfer vector across a vast expanse of respiratory epithelium. Surfactant, a naturally occurring protein and lipid mixture used to treat the respiratory distress syndrome of prematurity, disperses rapidly and eve...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.2-171
更新日期:1997-01-20 00:00:00
abstract::Based on the K8/JTS-1-mediated transfection technique, we developed an in vivo protocol for an efficient transfer of plasmid DNA to ocular cells. As determined with condensed plasmids containing reporter genes for either beta-galactosidase (pcDNA-lacZ) or enhanced green fluorescent protein (pREP-EGFP), the immortalize...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050129495
更新日期:2000-09-01 00:00:00
abstract::Extension of in vivo nucleic acid transfection techniques and increased information about those transfection properties and side effects are urgently needed to advance biological research and drug therapy. Tissue pressure-mediated transfection, involving lightly pressing the target tissue after intravenous injection o...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.213
更新日期:2009-10-01 00:00:00
abstract::As an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid DNA-cationic liposome complex. To explore whether this approach can be applied to the treatment of certain neurolo...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.7-1093
更新日期:1998-05-01 00:00:00
abstract::Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403321208998
更新日期:2003-03-01 00:00:00
abstract::Niemann-Pick type C (NP-C) disease is a neurodegenerative disorder characterized neuropathologically by ballooned neurons distended with lipid storage and widespread neuronal loss. Neural stem cells (NSC) derived from NP-C disease models have decreased ability for self-renewal and neuronal differentiation. Investigati...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2013.001
更新日期:2013-07-01 00:00:00
abstract::In vivo electroporation of plasmid DNA (DNA-EP) is an efficient and safe method for vaccines. It results in increased DNA uptake, enhances protein expression, and augments immune responses to the target antigen in a variety of species. To further improve the efficacy of DNA-EP, we evaluated small interfering RNA (siRN...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.210
更新日期:2009-06-01 00:00:00
abstract::The use of viral thymidine kinase (TK) gene coupled with the administration of ganciclovir to render cancer cell death has been studied extensively. Many of these experiments utilized retrovirus to transfer the TK gene under the control of a nonspecific promoter. Because nonspecific expression of the viral TK gene may...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.4-463
更新日期:1996-03-01 00:00:00