Abstract:
:The immune response against human immunodeficiency virus type-1 (HIV-1) is believed to play a role in controlling the early stages of disease progression. The cellular immune response, in particular cytotoxic T lymphocyte (CTL) activity, may be important for eliminating virally infected cells in HIV-1-infected individuals. Genetic immunization using retroviral vectors provides an effective means of introducing antigens into the antigen presentation pathways for T cell stimulation. A nonreplicating, amphotropic murine retroviral vector containing the HIV-1 IIIB env gene has been used to transduce primary rhesus monkey fibroblasts for the expression of HIV-1 antigenic determinants. Rhesus monkeys were immunized with four doses of either vector-transduced autologous fibroblasts (VTAF) expressing the HIV-1 IIIB ENV/REV proteins or nontransduced autologous fibroblasts (NTAF) administered at 2-week intervals. The animals were evaluated for both the induction of HIV-1-specific immune responses and potential toxicity associated with this ex vivo treatment. The VTAF-immunized monkeys generated CTL responses specific for HIV-1 ENV/REV expressing autologous target cells, whereas, NTAF-immunized monkeys showed negligible CTL activity. The cytotoxic activity was mediated by CD8+, major histocompatibility complex (MHC)-restricted CTL. In addition, antibody responses directed against the HIV-1 gp120 protein were also detected in the sera of VTAF-immunized monkeys. Clinical and histopathological evaluation of immunized monkeys showed no evidence of significant adverse events. Several animals that received either VTAF or NTAF had detectable anti-cytoplasmic antibodies, but were not positive for anti-nuclear antibodies or rheumatoid factor. Subsequent evaluation of renal, synovial, and hepatic tissue samples from these monkeys revealed no autoimmune disease-associated lesions. This study demonstrates the safety and ability of autologous retroviral vector-transduced cells expressing HIV-1 IIIB ENV/REV proteins to stimulate immune responses in a non-human primate model, and provides a basis for this form of genetic immunization in HIV-infected humans.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Laube LS,Burrascano M,Dejesus CE,Howard BD,Johnson MA,Lee WT,Lynn AE,Peters G,Ronlov GS,Townsend KSdoi
10.1089/hum.1994.5.7-853subject
Has Abstract,Author List Incompletepub_date
1994-07-01 00:00:00pages
853-62issue
7eissn
1043-0342issn
1557-7422journal_volume
5pub_type
杂志文章abstract::Adoptive cellular therapy provides the promise of a potentially powerful general treatment for cancer. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. However, these ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2010.086
更新日期:2010-06-01 00:00:00
abstract::RNA interference (RNAi) is an evolutionarily conserved mechanism of posttranscriptional gene-specific silencing. For in vivo applications, RNAi has been hampered until recently by inefficient delivery methods and by the transient nature of the gene suppression. Lentiviral vectors (LVs) hold great promise for gene ther...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403322611809
更新日期:2003-12-10 00:00:00
abstract::Here we show potent inhibition of HIV-1 replication in a human T cell line and primary human CD4(+) cells by expressing a single antiviral protein. Nullbasic is a mutant form of the HIV-1 Tat protein that was previously shown to strongly inhibit HIV-1 replication in nonhematopoietic cell lines by targeting three steps...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.176
更新日期:2013-03-01 00:00:00
abstract::Hematopoietic stem cells (HSCs) are a potential target for the retrovirus-mediated transfer of chemotherapeutic drug resistance genes. For integration of the proviral DNA in the HSC genome cell division is required. In the bone marrow (BM) hematopoiesis occurs in the vicinity of stroma cells. Soluble stroma components...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017789
更新日期:1999-06-10 00:00:00
abstract::Gene electrotransfer is gaining momentum as an efficient methodology for nonviral gene transfer. In skeletal muscle, data suggest that electric pulses play two roles: structurally permeabilizing the muscle fibers and electrophoretically supporting the migration of DNA toward or across the permeabilized membrane. To in...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hgt.2008.060
更新日期:2008-11-01 00:00:00
abstract::Adult T cell leukemia/lymphoma (ATL) is derived from CD4+ T cells and has a poor prognosis because of its resistance to chemotherapy. To evaluate the effectiveness of gene therapy for ATL, the effect of ganciclovir on ATL cell lines transfected with the thymidine kinase gene of herpes simplex virus type 1 (HSV-TK) was...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.18-2203
更新日期:1996-12-01 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::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::Accurate quantification of gene transfer (or gene correction) is a universal challenge in the field of gene therapy. In developing a clinical trial of lymphocyte gene therapy for Hunter syndrome (mucopolysaccharidosis type II), methods using Southern blot or automated DNA sequencing technology were employed, but found...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950016898
更新日期:1999-10-10 00:00:00
abstract::Skeletal muscle represents an attractive target tissue for adenoviral gene therapy to treat muscle disorders and as a production platform for systemic expression of therapeutic proteins. However, adenovirus serotype 5 vectors do not efficiently transduce adult muscle tissue. Here we evaluated whether capsid modificati...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.003
更新日期:2012-10-01 00:00:00
abstract::Low in vivo transduction efficiency and safety concerns have been hurdles for effective hematopoietic stem cell (HSC) gene therapy. Here, we investigate whether the safety and efficiency of retroviral gene transfer into HSCs can be improved by using human allogeneic umbilical cord blood (UCB)-derived supplements inste...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.123
更新日期:2008-07-01 00:00:00
abstract::Adrenomedullin (AM) has been shown to protect against ischemia/reperfusion-induced myocardial infarction and apoptosis. In the present study, we examined the potential neuroprotective action of delayed AM gene transfer in cerebral ischemia. Three days after a 1-hr occlusion of the middle cerebral artery (MCAO), rats w...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.1243
更新日期:2004-12-01 00:00:00
abstract::Aberrant JAK/STAT3 pathway has been reported to be related to hepatocellular carcinoma (HCC) in many cell lines. In this study, a double-regulated oncolytic adenovirus vector that can replicate and induce a cytopathic effect in alpha-fetoprotein (AFP)-positive HCC cell lines with p53 dysfunction was successfully const...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.219
更新日期:2011-09-01 00:00:00
abstract::Abstract Our studies have shown that coinjection of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors carrying the enhanced green fluorescent protein (EGFP) gene with self-complementary (sc) AAV2-T cell protein tyrosine phosphatase (TC-PTP) and scAAV2-protein phosphatase-5 (PP5) vectors resulted i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.100
更新日期:2010-03-01 00:00:00
abstract::CRISPR-based technology has been adapted to achieve a wide range of genome modifications including transcription regulation. The focus of this review is on the application of CRISPR-based platforms such as nuclease-deficient Cas9 and Cas12a, to achieve targeted gene activation. We review studies to date that have empl...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.241
更新日期:2021-01-15 00:00:00
abstract::Lentiviral vectors are efficiently pseudotyped with RD114-TR, a chimeric envelope glycoprotein made of the extracellular and transmembrane domains of the feline leukemia virus RD114 and the cytoplasmic tail of the murine leukemia virus amphotropic envelope. RD114-TR-pseudotyped vectors may be concentrated by centrifug...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.138
更新日期:2007-09-01 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::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::DNA expression vectors may be administered to patients like conventional medicines to have a finite and controlled duration of action. The clinical application of these medicines will require a precise understanding of the kinetics of the administered gene, the mRNA transcript, and the gene product. The apparent kinet...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1994.5.6-679
更新日期:1994-06-01 00:00:00
abstract::In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.046
更新日期:2016-12-01 00:00:00
abstract::Recombinant adeno-associated virus 2 (rAAV) vectors have been successfully used for sustained expression of therapeutic genes. The potential of using rAAV as a cancer vaccine vector and the impact of a bacterial plasmid adjuvant on this activity were investigated. C57BL/6 mice received a single intramuscular injection...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.856
更新日期:2004-09-01 00:00:00
abstract::Three dogs with deficiency of the lysosomal enzyme alpha-L-iduronidase were treated by gene replacement therapy targeted at muscle. Direct intramuscular injections of plasmid encoding the alpha-L-iduronidase gene cDNA resulted in no detectable enzyme production, but may have resulted in immunologic sensitization to id...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.13-1595
更新日期:1996-08-20 00:00:00
abstract::Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.129
更新日期:2009-01-01 00:00:00
abstract::Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, and even under optimal therapy these patients face a poor prognosis. Here we report a novel gene therapy-based strategy to battle this disease. We show that the majority of pancreatic tumors overexpress c-erb-B2, which therefor...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.083
更新日期:2010-02-01 00:00:00
abstract::Serum-induced inactivation of retroviruses is the most critical limitation for in vivo gene transfer therapy. To solve this problem, we searched for reagents that protect retroviruses from inactivation. The effects of the protease inhibitors FOY-007 and FOY-305 and of an inhibitor of the complement pathway FUT-175, al...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.13-1575
更新日期:1997-09-01 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::Duchenne muscular dystrophy (DMD) typically occurs as a result of truncating mutations in the DMD gene that result in a lack of expression of the dystrophin protein in muscle fibers. Various therapies under development are directed toward restoring dystrophin expression at the subsarcolemmal membrane, including gene t...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2013.092
更新日期:2013-09-01 00:00:00
abstract::This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via wee...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2010.020
更新日期:2010-09-01 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::The first report of in vivo gene delivery to the retina dates back to 1987 when a retroviral vector was injected intraocularly in newborn mice. Later came the observation that retinal cells could be successfully transduced using adenoviral and then adeno-associated and lentiviral vectors. By 2000, it had become clear ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.164
更新日期:2017-11-01 00:00:00