Abstract：
:Chimeric antigen receptor (CAR) T-cell therapies have demonstrated durable and potentially curative therapeutic efficacy against B-cell leukemia in clinical trials. A CAR strategy can target any tumor surface antigens as long as an antigen-binding receptor can be generated. New CARs that target solid tumors and have the potential to target multiple tumor types are needed. In this study, B7H6, a ligand for the NK cell activating receptor NKp30, was targeted to create a CAR that targets multiple tumor types. B7H6 is expressed on various primary human tumors, including leukemia, lymphoma and gastrointestinal stromal tumors, but it is not constitutively expressed on normal tissues. B7H6-specific CAR T cells have robust cellular cytotoxicity and interferon-γ secretion when co-cultured with B7H6+ tumor cells, and they exhibit little self-reactivity to immature dendritic cells or pro-inflammatory monocytes. In vivo, B7H6-specific CAR T cells greatly enhanced the survival of RMA/B7H6 lymphoma-bearing mice. The long-term survivor mice were protected against a B7H6-deficient tumor re-challenge. This CAR therapy also decreased tumor burden in a murine ovarian cancer model. In conclusion, B7H6-specific CARs have the potential to treat B7H6+ hematologic and solid tumors.
journal_name
Gene Therjournal_title
Gene therapyauthors
Wu MR,Zhang T,DeMars LR,Sentman CLdoi
10.1038/gt.2015.29subject
Has Abstractpub_date
2015-08-01 00:00:00pages
675-84issue
8eissn
0969-7128issn
1476-5462pii
gt201529journal_volume
22pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract：:Although most cases of tuberculosis (TB) can be cured with antibiotics, relapse is common if patients do not continue chemotherapy for at least 6 months. Thus, improved therapeutic strategies are urgently needed. We previously found that the combined DNA vaccine encoding the Mycobacterium tuberculosis proteins Ag85B, ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2008.13
更新日期：2008-05-01 00:00:00
abstract：:Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302644
更新日期：2006-02-01 00:00:00
abstract：:Synthetic oligonucleotides and DNA fragments of less than 1 kilobase (kb) have been shown to cause site-specific genetic alterations in mammalian cells in culture and in vivo. We have used a lacZ reporter gene system to compare the efficiency of episomal and chromosomal gene repair in human embryonic kidney epithelial...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302049
更新日期：2003-09-01 00:00:00
abstract：:We have constructed two recombinant adeno-associated virus (AAV) vectors (pJJ-3GC and pJJ-3ASA) which contained either the human glucocerebrosidase (GC) or arylsulfatase A (ASA) cDNA under the control of an SV40 promoter. These plasmids were co-transfected to 293 cells with a helper plasmid containing trans-acting AAV...
journal_title：Gene therapy
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:Polyethylenimine (PEI) has been studied as an efficient nonviral gene transfer vector. Here, we report the biodistribution fates and safety of plasmid DNA intravenously administered in PEI complexes. Using pCMVbeta as a model gene, the biodistribution of plasmid DNA was measured by quantitative polymerase chain reacti...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301516
更新日期：2001-10-01 00:00:00
abstract：:Adenoviral gene transfer to hematopoietic stem cells (HSCs)/progenitors would provide a new approach to the treatment of hematopoietic diseases and study of the hematopoietic system. We have previously reported that an adenovirus (Ad) vector composed of whole Ad serotype 35 (Ad35), which belongs to subgroup B, shows e...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302562
更新日期：2005-10-01 00:00:00
abstract：:Recently, there has been an increasing level of interest in electroporation for gene delivery due to the site-specific nature of the delivery, as well as the high efficiency of the method. Electroporation involves the application of a pulsed electric field to cells to enhance cell permeability, resulting in the transi...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301733
更新日期：2002-08-01 00:00:00
abstract：:Both replication-incompetent and replication-selective adenoviruses are being developed for the treatment of cancer and other diseases. Concerns have been raised about the safety of intra-vascular adenovirus administration following a patient death on a clinical trial with a replication-defective adenovirus. In additi...
journal_title：Gene therapy
pub_type： 临床试验,杂志文章
doi：10.1038/sj.gt.3301512
更新日期：2001-11-01 00:00:00
abstract：:Alphavirus vectors based on Sindbis virus and Semliki Forest virus (SFV) were characterized as potential gene transfer vectors. Initial studies were performed using vectors engineered to transfer either lacZ or green fluorescent protein (GFP). High levels of gene transfer were achieved in human primary fibroblasts, BH...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301122
更新日期：2000-03-01 00:00:00
abstract：:The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)bet...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301689
更新日期：2002-05-01 00:00:00
abstract：:We have designed new vectors for the construction of recombinant adenoviruses containing expression cassettes in the E1 and/or E3 regions. Using a versatile set of restriction enzymes, the cassettes are cloned into small bacterial vectors and subsequently introduced into large plasmids containing the adenoviral sequen...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301047
更新日期：2000-01-01 00:00:00
abstract：:This work demonstrates that electrical muscle stimulation markedly increases the transfection efficiency of an intramuscular injection of plasmid DNA. In soleus or extensor digitorum longus muscles of adult rats the percentage of transfected fibers increased from about 1 to more than 10. The number of transfected fibe...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300847
更新日期：1999-04-01 00:00:00
abstract：:Cationic lipid-based delivery systems such as lipoplexes or stabilized plasmid-lipid particles (SPLP) represent a safer alternative to viral systems for gene therapy applications. We studied the impact of cell cycle status on the efficiency of transfection of human ovarian carcinoma tumor cells using two cationic-lipi...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300837
更新日期：1999-03-01 00:00:00
abstract：:Current experimental gene therapy approaches for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) include the use of viral vectors expressing antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes. However, since increasing evidence favors a role for alpha-synuclein accumulation in the p...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302349
更新日期：2004-12-01 00:00:00
abstract：:Several of the current techniques for transfer of both oligonucleotide and plasmid DNA into the myocardium are impaired by low efficiency and toxicity. To improve gene transfer techniques, especially into the whole heart, a gene transfer method involving liposome in conjunction with a viral envelope (HVJ-liposome) was...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3300750
更新日期：1998-11-01 00:00:00
abstract：:The production of high-titer recombinant adeno-associated virus (rAAV) vector is essential for treatment of genetic diseases affecting the retina and choroid, where anatomical constraints may limit injectable volumes. Problematically, cytotoxicity arising from overexpression of the transgene during vector production f...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2017.50
更新日期：2017-08-01 00:00:00
abstract：:Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering RNAs (siRNAs) or DNA ...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302786
更新日期：2006-10-01 00:00:00
abstract：:The insertion of suicide genes in donor T lymphocytes constitutes the basis of new approaches aiming at the treatment of the graft-versus-host disease (GVHD), a frequent complication in recipients of allogeneic haematopoietic grafts. In this study we investigated the impact that the ex vivo manipulation required for t...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302188
更新日期：2004-03-01 00:00:00
abstract：:Prostate cancer is the most common cancer in men of the western world. To date, no effective treatment exists for metastatic prostate cancer and consequently, there is an urgent need to develop new and improved therapeutics. In recent years, the therapeutic potential of RNA interference (RNAi) has been extensively exp...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2015.50
更新日期：2015-10-01 00:00:00
abstract：:First-generation adenoviral (Ad) vectors are frequently used vectors for experimental and clinical gene transfer. Earlier it has been shown that parallel overexpression of the cell cycle regulator p21(Waf1/Cip1) (p21) or antiapoptotic bcl-2 from a second vector reduces cytotoxicity and improves transgene expression. H...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2009.2
更新日期：2009-04-01 00:00:00
abstract：:Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of P...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2009.117
更新日期：2010-01-01 00:00:00
abstract：:Mesenchymal stem cells (MSC) are a group of clonogenic cells present among the bone marrow stroma and capable of multilineage differentiation into mesoderm-type cells such as osteoblasts, adipocytes and chondrocytes. Due to their ease of isolation and their differentiation potential, MSC are being introduced into clin...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.gt.3303067
更新日期：2008-01-01 00:00:00
abstract：:In the last two decades, remarkable advances have been made in the development of technologies used to engineer new aptamers and ribozymes. This has encouraged interest among researchers who seek to create new types of gene-control systems that can be made to respond specifically to small-molecule signals. Validation ...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/gt.2009.81
更新日期：2009-10-01 00:00:00
abstract：:Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS), where suspected autoimmune attack causes nerve demyelination and progressive neurodegeneration and should benefit from both anti-inflammatory and neuroprotective strategies. Although neuroprotection strategies are relatively une...
journal_title：Gene therapy
pub_type： 杂志文章,评审
doi：10.1038/sj.gt.3302025
更新日期：2003-05-01 00:00:00
abstract：:Naturally occurring drug resistance genes of human origin can be exploited for selection of genetically engineered cells co-expressing a desired therapeutic transgene. Their non-immunogenicity in clinical applications would be a major asset. Human cytidine deaminase (hCD) is a chemoresistance gene that inactivates cyt...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301675
更新日期：2002-04-01 00:00:00
abstract：:Gene transfer vectors encoding two or more genes are potentially powerful research tools and are poised to play an increasingly important role in gene therapy applications. Common strategies employed to express more than one transgene per vector include the use of multiple promoters, internal ribosome entry site (IRES...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3303105
更新日期：2008-03-01 00:00:00
abstract：:Microwave (MW) energy consists of electric and magnetic fields and is able to penetrate deep into biological materials. We investigated the effect of MW (2450 MHz) irradiation on gene delivery in cultured mouse myoblasts and observed enhanced transgene expression. This effect is, however, highly variable and criticall...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/gt.2008.144
更新日期：2009-01-01 00:00:00
abstract：:The tumor-suppressor gene PTEN encodes a multifunctional phosphatase that is mutated in a variety of human cancers. PTEN inhibits the phosphatidylinositol 3-kinase pathway and downstream functions, including activation of Akt/protein kinase B (PKB), cell survival, and cell proliferation in tumor cells carrying mutant-...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3302100
更新日期：2003-11-01 00:00:00
abstract：:Hepatic fibrosis is a common outcome of chronic liver diseases. In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Recently, it has been shown that gene therapy is an attractive approach for the treatment of he...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301524
更新日期：2001-09-01 00:00:00
abstract：:Somatic gene transfer to the pulmonary endothelium may be a useful strategy for modifying the phenotype of endothelium and/or vascular smooth muscle in disorders such as primary pulmonary hypertension, ARDS or pulmonary metastatic disease. Adenoviral (Ad) vectors, although highly efficient in liver gene transfer, have...
journal_title：Gene therapy
pub_type： 杂志文章
doi：10.1038/sj.gt.3301636
更新日期：2002-02-01 00:00:00
