Abstract:
:Genetically modified lymphoblastoid cell lines (LCL) have been shown to be an attractive alternative source of antigen-presenting cells for cancer vaccination in vitro. We tested their application in patients with pancreatic cancer in a phase I clinical trial. As a model tumor antigen, we selected the point-mutated (codon 12) Ki-Ras p21 oncogene (muRas) frequently (∼85%) present in pancreatic adenocarcinoma. Autologous LCLs were established in vitro by spontaneous outgrowth from peripheral blood lymphocytes of seven pancreatic carcinoma patients and were genetically modified with an episomal Epstein-Barr virus (EBV)-based expression vector to express muRas (muRas-LCL). Weekly vaccinations with subcutaneous injection of 5×10(6) muRas-LCL were done. In six of seven patients, therapeutic vaccination elicited a T-cell response with an increase in the frequency of muRas-specific precursor cytotoxic T lymphocytes in the peripheral blood and positive delayed-type hypersensitivity reactions at the injection site. Besides local reactions and flu-like symptoms, there were no signs of toxicity and no acute EBV infection, onset of EBV-associated lymphoma, or other severe complications. A clinical response (stable disease) was observed for a short time period (2-4 months) in four of seven patients (57%), mostly in earlier tumor stages. Our results indicate that LCL presenting genetically modified antigen represent a valuable and easily available tool for in vivo autologous tumor vaccination. LCL can be transfected with any known tumor antigen and therefore should be further clinically investigated.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Kubuschok B,Pfreundschuh M,Breit R,Hartmann F,Sester M,Gärtner B,König J,Murawski N,Held G,Zwick C,Neumann Fdoi
10.1089/hum.2011.153subject
Has Abstractpub_date
2012-12-01 00:00:00pages
1224-36issue
12eissn
1043-0342issn
1557-7422journal_volume
23pub_type
临床试验,杂志文章abstract::Efficient DNA electrotransfer can be achieved with combinations of short high-voltage (HV) and long low voltage (LV) pulses that cover two effects of the pulses, namely, target cell electropermeabilization and DNA electrophoresis within the tissue. Because HV and LV can be delivered with a lag up to 3000 sec between t...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.1194
更新日期:2005-10-01 00:00:00
abstract::La Crosse virus (LACV)-mediated encephalitis is the most frequently reported arboviral disease in the United States, but to date no vaccine against this virus is available. We have established a new animal model, genetically targeted mice lacking a functional interferon type I receptor (IFNAR-1). These mice show an ag...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017653
更新日期:1999-07-01 00:00:00
abstract::MDA-MB-231, an HLA-A2(+), HER2/neu(+) allogeneic breast cancer cell line genetically modified to express the costimulatory molecule CD80 (B7-1), was used to vaccinate 30 women with previously treated stage IV breast cancer. Expression of CD80 conferred the ability to deliver a costimulatory signal and thereby improved...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/104303403322124828
更新日期:2003-07-20 00:00:00
abstract::Aerosol delivery of adenoviral vectors is of particular interest in regard to gene therapy for cystic fibrosis (CF), with potential advantages of more uniform respiratory delivery, a less invasive approach, and ease of repetition. The AdHCMVsp1LacZ (AdLacZ) adenoviral vector was used to evaluate the feasibility of aer...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.8-985
更新日期:1995-08-01 00:00:00
abstract::The recombinant adenoviral (Ad) vector is being considered as a cancer vaccine platform because it efficiently induces immune responses to tumor antigens by intradermal immunization. The aims of this study were to evaluate the potential toxicities and biodistribution after a single dose or six weekly intradermal doses...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.705
更新日期:2006-07-01 00:00:00
abstract::Mutations in the gene encoding the peroxisomal ATP-binding cassette transporter (ABCD1) cause elevations in very long-chain fatty acids (VLCFAs) and the neurodegenerative disease adrenoleukodystrophy (ALD). In most adults, this manifests as the spinal cord axonopathy adrenomyeloneuropathy (AMN). A challenge in virus-b...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.079
更新日期:2019-05-01 00:00:00
abstract::The rapid inactivation of murine-derived retroviral vectors in human or nonhuman primate sera is largely attributed to the activity of complement mediated through the classical pathway. In this study, we have further investigated the relationship between the human complement cascade and retrovirus inactivation. Preinc...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.4-429
更新日期:1995-04-01 00:00:00
abstract::Rat myoblast primary cultures were tested as a model for proinsulin synthesis and processing and unregulated insulin delivery for insulin-dependent diabetes mellitus (IDDM) gene therapy. Three human proinsulin cDNA constructs containing genetically engineered furin endoprotease cleavage sites between the B-chain and C...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.1-71
更新日期:1996-01-01 00:00:00
abstract::Hemophilia arthropathy (HA) represents the majority of morbidity in severe hemophilia patients, especially in resource-limited countries. Adeno-associated virus (AAV)-mediated gene therapy is showing promise for managing hemophilia. However, patients with neutralizing antibodies (NAbs) against AAV, and inhibitors to c...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.355
更新日期:2020-04-01 00:00:00
abstract::Combining chemotherapy and immunotherapy is problematic because chemotherapy can ablate the immune responses initiated by modulators of the immune system. We hypothesized that protection of immunocompetent cells from the toxic effects of chemotherapy, using drug resistance gene therapy strategies, would allow the comb...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.798
更新日期:2006-08-01 00:00:00
abstract::Adenoviral vectors used in gene therapy are predominantly derived from adenovirus serotype 5 (Ad5), which infects a broad range of cells. Ad5 cell entry involves interactions with the coxsackie-adenovirus receptor (CAR) and integrins. To assess these receptors in vivo, we mutated amino acid residues in fiber and pento...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403765255165
更新日期:2003-05-20 00:00:00
abstract::Administration of recombinant adenoviral (AdV) vectors to animals can lead to inflammatory and immune responses. For therapeutic indications in which repeated treatment is necessary, such as cystic fibrosis (CF), these responses can limit the therapeutic usefulness of the vector. In principle, the utility of the vecto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401300042348
更新日期:2001-03-20 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::Adenovirus-based vectors comprise the most frequently used vector type in clinical studies to date. Both intense lab research and insights from the clinical trials reveal the importance of a comprehensive understanding of vector-host interactions. Especially for systemic intravenous adenovirus vector delivery, it is p...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2017.139
更新日期:2017-10-01 00:00:00
abstract::The in vitro genetic manipulation of dendritic cells (DCs) for the expression of foreign proteins or peptides will assist in the development of immunotherapeutic approaches to treat cancer, immunological disorders, and/or infectious diseases. Reports have shown the expansion and differentiation of CD34(+) progenitor c...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050207975
更新日期:2000-12-10 00:00:00
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 tw...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750270922
更新日期:2001-07-01 00:00:00
abstract::Despite improvements in drug and device therapy for heart failure, hospitalization rates and mortality have changed little in the past decade. Randomized clinical trials using gene transfer to improve function of the failing heart are the focus of this review. Four randomized clinical trials of gene transfer in heart ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2016.166
更新日期:2017-05-01 00:00:00
abstract::An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to p...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.945
更新日期:2004-10-01 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::To evaluate the hypothesis that innate immune mechanisms play a major role in eliminating adenovirus (Ad) vectors from the lung, the fate of adenoviral genome of an Ad vector was quantified in the first 24 h after intratracheal administration of an Ad vector coding for beta-galactosidase (beta gal) to mice. Southern a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.14-1675
更新日期:1997-09-20 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::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::When transferring the human multidrug resistance 1 (MDR1) cDNA, FMEV retroviral vectors mediate high-dose multidrug resistance and, thus, background-free selection in primary human hematopoietic progenitor cells. Here, we analyzed strategies for co-expression of a second gene from an FMEV:MDR1 vector. When linking the...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.1-33
更新日期:1998-01-01 00:00:00
abstract::Human hematopoietic stem cells (HSCs) are poorly transduced by vectors based on adenovirus serotype 5 (Ad5). This is primarily due to the paucity of the coxsackievirus-Ad receptor on these cells. In an attempt to change the tropism of Ad5, we constructed a series of chimeric E1-deleted Ad5 vectors in which the shaft a...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401753204562
更新日期:2001-11-01 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::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::Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of human airway epithelia. The packaging of a recombinant adeno-associated virus 2 (rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that also efficiently transduces human airway epithelia. As such, this vector is attract...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2017.060
更新日期:2017-08-01 00:00:00
abstract::A novel retroviral vector has been designed based on a Friend-murine leukemia virus (Fr-MuLV) FB29 strain. The latter has been selected according to characteristics of pathogenicity in mice where it induces a disease of the haemopoietic system affecting all lineages. Higher infectivity has also been demonstrated as co...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.2-207
更新日期:1998-01-20 00:00:00
abstract::We evaluated the efficiency of gene transduction and of gene expression by adenoviral vectors in human lung adenocarcinoma cells. Freshly isolated cancer cells were collected from pleural effusions in adenocarcinoma patients by centrifugation with a Percoll gradient. Adenoviral vectors resulted in effective gene trans...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.1-1
更新日期:1997-01-01 00:00:00
abstract::Interleukin (IL)-12 has been reported to induce cellular immune responses for protection against tumor formation. Here we investigate the utility of adenoviral delivery of IL-12 as an adjuvant for a human papillomavirus E7 subunit vaccine in a mouse tumor challenge model. Direct intratumoral injection of AdIL-12 resul...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403769211619
更新日期:2003-10-10 00:00:00