Abstract:
:We report on an antitumor treatment involving electrogene therapy (EGT), a newly developed in vivo gene transfer method using electroporation. We carried out in vivo EGT in a subcutaneous model of CT26 colon carcinoma cells, using plasmid DNAs encoding interleukin 12 (IL-12) subunits. For this purpose, we developed two IL-12 expression systems: a cotransfer system using a plasmid encoding the IL-12 p40 subunit and a plasmid encoding the IL-12 p35 subunit, and a single-vector system using a plasmid expressing a p40-p35 fusion protein. Both transfer systems significantly inhibited the growth of CT26 tumor. Immunohistochemical analysis of IL-12 EGT-treated tumors revealed enhanced infiltration of CD8(+) cells into the tumor tissue, while reverse transcriptase-polymerase chain reaction confirmed the increased expression of interferon gamma within treated tumors. The same IL-12 EGT applied to the nude mouse model was not effective, suggesting the critical role of T cell infiltration in this treatment. The inhibitory effects revealed in experiments in which previously treated mice were rechallenged with a second inoculation of CT26 tumor cells suggested that IL-12 EGT may also establish partial systemic antitumor immunity. The growth of IL-12 EGT-treated Renca tumors, a renal cell carcinoma, was also significantly inhibited. These findings suggest that EGT of the IL-12 gene has the potential to be an effective anticancer gene therapy.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Tamura T,Nishi T,Goto T,Takeshima H,Dev SB,Ushio Y,Sakata Tdoi
10.1089/104303401750270922keywords:
subject
Has Abstractpub_date
2001-07-01 00:00:00pages
1265-76issue
10eissn
1043-0342issn
1557-7422journal_volume
12pub_type
杂志文章abstract::Recombinant adeno-associated virus 2 (rAAV2) has been extensively used as a gene delivery vector for the nervous system. It targets primarily neurons in the nervous system and results in sustained long-term expression of transgenes. New rAAV serotypes have been characterized and demonstrated to have improved transduct...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2005.16.781
更新日期:2005-07-01 00:00:00
abstract::Oncolytic viruses (OV) are novel cancer gene therapies that are moving toward the forefront of modern medicines. However, their full therapeutic potential is hindered by the lack of convenient and reliable strategies to visualize and quantify OV growth kinetics and therapeutic efficacy in live cells. Here, we present ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.294
更新日期:2021-01-27 00:00:00
abstract::Human papillomavirus type 16 (HPV16) is associated with the development of anogenital cancers and their precursor lesions, intraepithelial neoplasia. Treatment strategies against HPV-induced intraepithelial neoplasia are not HPV specific and mostly consist of physical removal or ablation of lesions. We had previously ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.115
更新日期:2010-07-01 00:00:00
abstract::Retrovirus integration into the host cell genome occurs most efficiently in replicating cells. In agreement with this notion, it was observed that the efficiency with which hemopoietic stem cells (HSC) can be transduced is greatly enhanced when the hemopoietic growth factor (HGF) interleukin 3 (IL-3) is added to co-cu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1991.2.4-301
更新日期:1991-01-01 00:00:00
abstract::Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a devastating disease caused by mutations in TYMP, which encodes thymidine phosphorylase (TP). In MNGIE patients, TP dysfunction results in systemic thymidine and deoxyuridine overload, which interferes with mitochondrial DNA replication. Preclinical stu...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.217
更新日期:2019-08-01 00:00:00
abstract::Recombinant adeno-associated virus (rAAV) is a prototypical gene therapy vector characterized by excellent safety profiles, wide host range, and the ability to transduce differentiated cells. Numerous rAAV-based vectors providing efficient and sustained expression of transgenes in target tissues have been developed fo...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2005.16.551
更新日期:2005-05-01 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::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::Conditionally replicative adenovirus (CRAd) vectors are designed for specific oncolytic replication in tumor tissues with concomitant sparing of normal cells. As such, CRAds offer an unprecedented level of anticancer potential for malignancies that have been refractory to previous cancer gene therapy interventions. CR...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340152710504
更新日期:2001-12-10 00:00:00
abstract::Gene transfer of the herpes simplex virus thymidine kinase (TK) gene associated with ganciclovir (GCV) treatment can lead to death of TK-expressing cells, and of neighboring TK- cells because of the bystander effect. Thus, a small proportion of TK+ cells in a tumor can lead to its complete regression after GCV treatme...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050083298
更新日期:2000-07-20 00:00:00
abstract::The combination of immunization strategies with gene therapy methods constitutes a powerful tool for the purpose of genetic immunization. The cutaneous microenvironment, rich in professional antigen-presenting cells and accessory cells capable of initiating and controlling the intensity of specific immune responses, m...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/104303400750035852
更新日期:2000-11-01 00:00:00
abstract::In the next decades, gene editing technologies are expected to be used in the treatment and prevention of human diseases. Yet, the future uses of gene editing in medicine are still unknown, including its applicability and effectiveness to the treatment and prevention of infectious diseases, cancer, and monogenic and p...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.136
更新日期:2020-08-01 00:00:00
abstract::Engineering gene therapy vectors to modulate the immune response is an important goal. In this regard, costimulation of T cells is a critical determinant in immune activation. The costimulatory molecule CD40, expressed on antigen-presenting cells, is thought to interact with CD40 ligand (CD40L) expressed on activated ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750214302
更新日期:2001-06-10 00:00:00
abstract::Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limit...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2014.001
更新日期:2014-04-01 00:00:00
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::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::Trans-dominant mutants of human immunodeficiency virus type 1 (HIV-1) Tat and Rev are attractive candidates for use in gene therapy in the treatment of HIV-1 infections because both are essential for viral replication. Retroviral vectors were constructed to allow either Tat-inducible or Tat- and Rev-inducible expressi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.5-625
更新日期:1993-10-01 00:00:00
abstract::Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.4-487
更新日期:1998-03-01 00:00:00
abstract::Gyrate atrophy is a progressive blindness associated with deficiency of ornithine aminotransferase (OAT). The strategy of using an autologous keratinocyte graft, modified to express high levels of OAT as an ornithine-catabolizing skin-based enzyme sink, is investigated. Two OAT-containing retroviral vectors were const...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.17-2125
更新日期:1997-11-20 00:00:00
abstract::Cell-based gene transfer using a stent platform would provide a significant advantage in terms of site-specific gene expression in the vasculature. The current study presents a novel stent design that allows stable in vivo transgene expression over a 4-week period in the vasculature. A mesh-stent coated with fibronect...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252792567
更新日期:2002-02-10 00:00:00
abstract::Airway infiltration by eosinophils is a major characteristic of chronic asthma. CCL11 (eotaxin-1) is secreted by lung epithelial cells and functions as the major chemokine for eosinophil recruitment. Pseudotyped adeno-associated virus (AAV) 2/9, composed by the AAV2 rep and AAV9 cap genes, can efficiently target lung ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.012
更新日期:2012-11-01 00:00:00
abstract::Clinical gene transfer research has involved adult and child subjects, and it is expected that gene transfer in fetal subjects will occur in the future. Some genetic diseases have serious adverse effects on the fetus before birth, and there is hope that prenatal gene therapy could prevent such disease progression. Res...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.062
更新日期:2011-11-01 00:00:00
abstract::Gene therapy for Duchenne muscular dystrophy will likely require that the corrective dystrophin gene be delivered to a high fraction of muscle fibers in vivo. Because of the large size of the dystrophin cDNA, adenoviral (Ad) vectors have been developed for this application. However, Ad vectors transduce mature muscle ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.314
更新日期:2006-03-01 00:00:00
abstract::NKG2D ligands (NKG2DLs) are widely expressed on ovarian cancers to various degrees, making them attractive targets for immunotherapy. Here, we applied a chimeric antigen receptor (CAR) approach for the targeting of NKG2DLs expressed on human ovarian cancer cells and evaluated the impact of pharmacological upregulation...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.143
更新日期:2013-03-01 00:00:00
abstract::Kallistatin is a serine proteinase inhibitor that has been shown to reduce joint swelling and to inhibit inflammation in a rat model of arthritis. In this study, we investigated the effect and mechanisms of kallistatin on cardiac function after myocardial ischemia-reperfusion (I/R) injury. The human kallistatin gene i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.1201
更新日期:2006-12-01 00:00:00
abstract::Traditionally, skeletal muscle and liver are the preferred target organs for gene transfer to supply a transgene product into the systemic circulation. In this respect, adipose tissue presents a number of attractive features. However, adipose tissue transduction in vivo has not been feasible by conventional methods. T...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.921
更新日期:2006-09-01 00:00:00
abstract::The therapeutic use of neurotrophic factors for neurodegenerative diseases is promising, however, optimal methods for continuous delivery of these substances to the human central nervous system (CNS) remains problematic. One approach would be to graft genetically engineered human cells that continuously secrete high l...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.3-331
更新日期:1997-02-10 00:00:00
abstract::The transfer of a drug resistance gene into hematopoietic cells is an approach being investigated to overcome the problem of myelosuppression produced by anticancer drugs. Chemotherapeutic agents are often given in combination in order to increase their effectiveness. Consequently, there is an advantage in designing v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.17-2537
更新日期:1998-11-20 00:00:00
abstract::Fibroblast-like synoviocytes (FLSs) participate in the pathogenesis of rheumatoid arthritis (RA). Emerging evidence has highlighted the role of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and its potential involvement in RA. In this study, we test the hypothesis that the MALAT1 ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.212
更新日期:2019-08-01 00:00:00
abstract::Adenovirus type 5 (Ad5) is a commonly used vector for gene therapy, but its efficacy is limited by high seroprevalence and off-target hepatic and splenic sequestration. In order to circumvent these limitations, the use of vectors derived from rare species adenoviruses is appealing. The opportunity to retarget rare spe...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2014.016
更新日期:2014-04-01 00:00:00