Abstract:
:Immune responses to tumor-associated antigens are often dampened by a tumor-induced state of immune anergy. Previous work has attempted to overcome tumor-induced T-cell anergy by the direct injection of vectors carrying the genes encoding one of a variety of cytokines. We hypothesised that the polyclonal stimulation of T cells, preferably through the TCR complex, would result in a cascade of cytokines associated with T-cell activation and would be best able to overcome T-cell anergy. Here we use the highly attenuated MVA poxvirus to express on tumor cells, in vitro and in vivo, either of three membrane-bound monoclonal antibodies specific for murine TCR complex. Using this system, we have expressed antibodies specific for the CD3 epsilon chain (KT3), TCR alpha/beta complex (H57-597), and V beta 7 chain (TR310). Tumor cells bristling with these antibodies are capable of inducing murine T-cell proliferation and cytokine production. When injected into growing tumors (P815, RenCa, and B16F10), these constructs induce the activation of immune effector cells and result in the rejection of the tumor. Histological and FACS analysis of tumor-infiltrating leukocytes reveal that the injection of recombinant virus-expressing antibodies specific for the TCR complex attracts and activates (CD25(+), CD69(+)) CD4 and CD8 lymphocytes. This approach represents a novel strategy to overcome T-cell anergy in tumors and allow the stimulation of tumor-specific T cells.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Paul S,Regulier E,Rooke R,Stoeckel F,Geist M,Homann H,Balloul JM,Villeval D,Poitevin Y,Kieny MP,Acres RBdoi
10.1038/sj.cgt.7700461subject
Has Abstractpub_date
2002-05-01 00:00:00pages
470-7issue
5eissn
0929-1903issn
1476-5500journal_volume
9pub_type
杂志文章abstract::Inflammation, among environmental risk factors, is one of the most important contributors to colorectal cancer (CRC) development. In this way, studies revealed that the incidence of CRC in inflammatory bowel disease patients is up to 60% higher than the general population. MicroRNAs (miRNAs), small noncoding RNA molec...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41417-020-0172-0
更新日期:2020-11-01 00:00:00
abstract::Prostate cancer is one of the most commonly diagnosed cancers and the second leading cause of cancer deaths in Americans. The high mortality rate is mainly attributed to the invasiveness and metastasis of advanced prostate cancer. Targeting the molecules involved in metastasis could be an effective mode of treatment f...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.16
更新日期:2010-09-01 00:00:00
abstract::Colon carcinoma accounts for 20% of deaths due to malignancies in the Western world. Once metastases occur, therapeutic options are limited, with an approximate 5-year survival of only 5%. To investigate the potential of new gene therapeutic approaches, a hepatic micrometastasis model of colon carcinoma in BALB/c mice...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700131
更新日期:2000-03-01 00:00:00
abstract::Replication-selective oncolytic viruses are being developed for human cancer therapy. We previously developed an attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site. OBP-301...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.57
更新日期:2012-11-01 00:00:00
abstract::The purpose of this study was to determine the feasibility of cytokine gene delivery to lymphatic tissue using transduced bone marrow-derived cells. MBAE and pBABE retroviral vectors carrying the genes for murine interleukin-4 and the selection marker neomycin phosphotransferase (neo) were used to transduce bone marro...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700204
更新日期:2000-08-01 00:00:00
abstract::Screening and identifying molecules target to checkpoint pathways has fostered the development of checkpoint-based anticancer strategies. Among these targets, inhibition of chk2 may induce cell death for tumors whose growth depends on enhanced chk2 activity. However, improvement of the potency and specificity of such ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700967
更新日期:2006-10-01 00:00:00
abstract::Glioblastoma (GBM) is by far the most common and the most aggressive of all the primary brain malignancies. No curative therapy exists, and median life expectancy hovers at around 1 year after diagnosis, with a minute fraction surviving beyond 5 years. The difficulty in treating GBM lies in the cancer's protected nich...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2016.46
更新日期:2017-03-01 00:00:00
abstract::As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.cgt.7700965
更新日期:2006-12-01 00:00:00
abstract::Lung metastases are a frequent complication of osteosarcoma and a treatment that would reduce the severity of this complication would be of great benefit to patients. We have used a formulation consisting of polyethyleneimine (PEI) and a p53 gene administered in aerosol to treat established lung micrometastases as a m...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700343
更新日期:2001-09-01 00:00:00
abstract::We aimed to analyze the association between the distribution of dendritic cells (DC) with expression of tumor-infiltrating T lymphocytes and clinicopathologic parameters with prognosis in epithelial ovarian cancer (EOC). Thirty-three EOC patient samples were surgically resected, and pathology was examined for clinicop...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2015.7
更新日期:2015-03-01 00:00:00
abstract::Transfer of genes to the gastrointestinal epithelium would be advantageous from investigational and therapeutic standpoints. Efficient transfer of DNA to the intestinal epithelial cells, however, has been problematic with conventional viral and nonviral vectors. As an alternative, we have utilized molecular conjugate ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Multiple myeloma (MM) accounts for 10% of hematological malignant disorders. Its refractory nature indicates the necessity of developing novel therapeutic modalities. Since interleukin 6 (IL-6) is one of the major growth factors for MM cells, we expressed suppressor of cytokine signaling-1 (SOCS-1), one of the blockad...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700873
更新日期:2006-02-01 00:00:00
abstract::Sarcomas, or tumors of connective tissue, represent roughly 20% of childhood cancers. Although the cure rate for sarcomas in general has significantly improved in the last 10 years, there continue to be subgroups that are difficult to treat. High-grade or metastatic soft-tissue sarcomas and rhabdomyosarcomas (RMS) of ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700798
更新日期:2005-04-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) is one of the most widely studied viruses for oncolytic virotherapy. In squamous cell carcinoma (SCC) cells, the role of autophagy induced by neurovirulence gene-deficient HSV-1s in programmed cell death has not yet been elucidated. The oncolytic HSV-1 strain RH2, which lacks the γ3...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2017.33
更新日期:2017-09-01 00:00:00
abstract::The herpes simplex virus thymidine kinase gene (HSV-TK) in combination with ganciclovir (GCV), is currently being used in gene therapy-based clinical trials for cancer treatment. Its therapeutic effect is based on a "bystander effect" whereby HSV-TK gene-modified tumor cells are toxic to nearby unmodified tumor cells ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::Sodium iodide symporter (NIS) reporter gene imaging is an excellent technology for noninvasive cell fate determination in living animals unless the NIS-transduced cells reside in perigastric organs such as the spleen, liver, diaphragm, omentum, pancreas, perigastric lymph nodes or perigastric tumor deposits. Here we r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.57
更新日期:2013-11-01 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-beta by malignant cells may therefore be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In order to evaluate the role of tumor-derived TGF-beta on tumor...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Nuclear factor-kappa B (NF-κB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-κB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-κB has been developed. To determin...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.75
更新日期:2011-04-01 00:00:00
abstract::Malignant tumors express tumor-related antigens, but effective antitumor immunity does not occur in the primary host. One hypothesis is that there is insufficient stimulation of T-cell responses due to ineffective antigen presentation. An approach to overcome these deficiencies is to modify tumor cells to express majo...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::The zinc-fingers and homeoboxes (ZHX) family is a group of nuclear homodimeric transcriptional repressors that interact with a subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. The members of ZHX family form homodimers or heterodimers with other members o...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2015.16
更新日期:2015-05-01 00:00:00
abstract::Gene therapy for prostate cancer may be realized through transduction of whole genes, such as PSA or PSMA, into immunotherapeutic dendritic cells (DCs). An oncoretroviral vector encoding human PSMA and a bicistronic oncoretroviral vector encoding human PSA and cell surface CD25 cDNAs were constructed. Remarkably, tran...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700810
更新日期:2005-06-01 00:00:00
abstract::Stathmin is the founding member of a family of microtubule-destabilizing proteins that have a critical role in the regulation of mitosis. Stathmin is expressed at high levels in breast cancer and its overexpression is linked to disease progression. Although there is a large body of evidence to support a role for stath...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.21
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abstract::Cancer is one of the main problems in public health worldwide. Despite rapid advances in the diagnosis and treatment of cancer, the efficacy of current treatment strategies is still limited. There are promising new results in animal models whereby mesenchymal stem cells (MSCs) can be used as vehicles for targeted ther...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2016.35
更新日期:2016-09-01 00:00:00
abstract::We have developed unique replication-competent retroviral (RCR) vectors based on murine leukemia virus that provide improved efficiency of viral delivery, allow for long-term transgene expression and demonstrate an intrinsic selectivity for transduction of rapidly dividing tumor cells. The purpose of this study was to...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7701013
更新日期:2007-03-01 00:00:00
abstract::Interferon-gamma (IFN-γ) exhibits biological activities that are considered to have important roles in tumor suppression. Therefore, the IFN-γ gene is a potential candidate for in vivo cytokine gene therapy against skin cancer. The present study evaluated the efficacy of a hydrodynamics-based IFN-γ gene transfection f...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.36
更新日期:2011-09-01 00:00:00
abstract::A nonviral gene delivery vector has been developed in our laboratory based on the cationic polymer, poly(2-(dimethylethylamino)ethyl methacrylate) (p(DMAEMA)). p(DMAEMA)-based polyplexes have been successfully used for the transfection of OVCAR-3 cells in vitro. However, these polyplexes were unable to transfect OVCAR...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700311
更新日期:2001-06-01 00:00:00
abstract::Recurrent fusion genes (FGs) with clinical significances in leukemias are mainly mutually exclusive, and the coexistence of different FGs has been rarely reported. In this study, we retrospectively analyzed the incidence, genetic characteristics, and prognosis of leukemias with concurrent pathogenic FGs, which commonl...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0147-1
更新日期:2020-02-01 00:00:00
abstract::Cationic liposomes have been shown to potentiate markedly the ability of plasmid DNA to activate innate immune responses. We reasoned therefore that liposome-DNA complexes (LDC) could be used to produce more effective plasmid DNA vaccines for cancer. To test this hypothesis, tumor-bearing mice were vaccinated with con...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700982
更新日期:2006-11-01 00:00:00
abstract::Angiogenesis is among the most important mechanisms that helps cancer cells to survive, grow and undergo metastasis. Therefore, inhibiting angiogenesis will suppress tumor growth. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are believed to be important players of angiogenesis. The goal of this s...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.76
更新日期:2017-01-01 00:00:00
abstract::Adenoviral vectors are widely used in cancer gene therapy. After systemic administration however, the majority of the virus homes to the liver and the expressed transgene may cause hepatotoxicity. To restrict transgene expression to tumor cells, tumor- or tissue-specific promoters are utilized. The tumor antigen epith...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700882
更新日期:2006-02-01 00:00:00