Abstract：
:T-cell receptor (TCR) gene transfer for cancer immunotherapy is limited by the availability of large numbers of tumor-specific T cells. TCR alpha and beta chains were isolated from a highly lytic HLA-A2-restricted cytotoxic T lymphocyte (CTL) clone recognizing the melanoma-associated Melan-A/MART-1 antigen and inserted into a lentiviral vector carrying a bidirectional promoter capable of robust and coordinated expression of the two transgenes. Lentiviral vector-based gene delivery systems have shown increased transfer efficiency and transgene expression compared with the widely used gamma-retroviral vectors. This vector performed more efficiently than a gamma-retrovirus-based vector containing the same expression cassette, resulting in a T-cell population with 60% to 80% of transgenic TCR expression with mainly CD8(+) intermediate effector phenotype. Transgenic T cells specifically produced cytokine in response to and killed antigen-expressing melanoma cells, retained an overlapping functional avidity in comparison with the TCR donor CTL clone, and exerted significant therapeutic effects in vivo upon adoptive transfer in melanoma-bearing severe combined immunodeficient mice. Optical imaging showed their accumulation in the tumor site. Overall, our results indicate that lentiviral vectors represent a valid tool for stable and high-intensity expression of transgenic TCR and support clinical exploitation of this approach for therapeutic application.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Bobisse S,Rondina M,Merlo A,Tisato V,Mandruzzato S,Amendola M,Naldini L,Willemsen RA,Debets R,Zanovello P,Rosato Adoi
10.1158/0008-5472.CAN-09-0494subject
Has Abstractpub_date
2009-12-15 00:00:00pages
9385-94issue
24eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-09-0494journal_volume
69pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:: Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show that two p53-responsive miRNAs utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilizat...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-1886
更新日期：2018-12-01 00:00:00
abstract：:MdmX and Mdm2 regulate p53 tumor suppressor functions by controlling p53 transcriptional activity and/or stability in cells exposed to DNA damage. Accumulating evidence indicates that ATM-mediated phosphorylation and degradation of Mdm2 and MdmX may be the initial driving force that induces p53 activity during the ear...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-0634
更新日期：2009-10-15 00:00:00
abstract：:MUC1 is a heterodimeric transmembrane glycoprotein that is overexpressed and aberrantly glycosylated in ductal adenocarcinomas. Differential phosphorylation of the MUC1 cytoplasmic tail (MUC1CT) has been associated with signaling events that influence the proliferation and metastasis of cancer cells. We identified a n...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4647
更新日期：2007-06-01 00:00:00
abstract：:The pharmacokinetic disposition of tiazofurin in plasma and cerebrospinal fluid was examined in rhesus monkeys. Tiazofurin was readily detectable in both plasma and cerebrospinal fluid within 20 min of commencement and for 24 h after a short i.v. infusion of the drug. The mean clearance of tiazofurin from plasma was 7...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-05-01 00:00:00
abstract：:Tumor production of parathyroid hormone-related protein (PTHRP) is responsible for most cases of hypercalcemia of malignancy. The transplantable rat Leydig tumor H-500 is known to cause hypercalcemia in rats by the release of abundant PTHRP and to closely reproduce the human syndrome. We have demonstrated recently tha...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-03-15 00:00:00
abstract：:Epstein-Barr virus (EBV) infection is associated with immunoblastic B-cell lymphomas in immunosuppressed or human immunodeficiency virus-infected individuals and in SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors. The risk of tumors appearing in the hu-PBL-SCID...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:T cells expressing human leukemia virus (HTLV) type 1, the etiological agent of adult T-cell leukemia, are remarkably resistant to conventional chemotherapy, and the need for drugs that effectively kill these cells is apparent. Here we show that roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), induces the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-12-01 00:00:00
abstract：:Between June 1977 and December 1979, 72 evaluable patients with childhood non-T-cell acute lymphoblastic leukemia were induced into complete remission using vincristine, prednisone, and doxorubicin. All received asparaginase consolidation and central nervous system prophylaxis with cranial irradiation and intrathecal ...
journal_title：Cancer research
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1983-11-01 00:00:00
abstract：:Structural alterations of the p53 gene were investigated in tissue specimens of gastric and cervical cancers and in cell lines of gastric, esophageal, and cervical cancers, by polymerase chain reaction-single-strand conformation polymorphism analysis. Two of the four gastric cancer metastases and four of the eight cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Recently we have reported synergistic effects between glycine-extended gastrin (G-gly) and amidated gastrin-17 on acid secretion in short-term infusion studies. In the present study, we examined the long-term effect of G-gly on the atrophy-promoting effects of amidated gastrin in the mouse stomach with or without Heli...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-0876
更新日期：2004-11-15 00:00:00
abstract：:The correlation between telomerase activity, telomere lengths, and cellular replicative capacity has led to the theory that maintenance of telomere lengths by telomerase acts as a molecular clock to control replicative capacity and senescence. Regulation of this molecular clock may have applications in the treatment o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-09-15 00:00:00
abstract：:Von Hippel-Lindau (VHL) tumor suppressor protein is expressed in neurons of the central nervous system and plays an important role during the neuronal differentiation of central nervous system progenitor cells. To elucidate the neuronal differentiating potential of VHL protein in neuroblastoma cells, we overexpressed ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-12-01 00:00:00
abstract：:Aldophosphamide (NSC 254), a putative key metabolite of cyclophosphamide, has now been isolated as a cyanohydrin derivative from an incubation mixture of cyclophosphamide with mouse liver microsomes in vitro and from the plasma of a cyclophosphamide-treated patient. The cyanohydrin has been shown to be identical with ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-08-01 00:00:00
abstract：:We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput metho...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-03-0932
更新日期：2004-08-01 00:00:00
abstract：:The human papillomavirus (HPV) 16 E7 oncoprotein has been reported previously to stimulate DNA damage and to activate host cell DNA damage checkpoints. How HPV-16 E7 maintains proliferation despite activated DNA damage checkpoints is incompletely understood. Here, we provide evidence that cells expressing the HPV-16 E...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-0925
更新日期：2009-09-01 00:00:00
abstract：:Initial rates of [3H]adenosine diphosphate and [3H]adenosine triphosphate uptake were measured in mitochondria isolated from normal rat liver, regenerating liver, mouse hepatoma BW7756, and four Morris hepatomas (7777, 7800, 7794A, and 16) of varying degrees of malignancy. Results obtained demonstrate that (a) the app...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-04-01 00:00:00
abstract：:Anti-inflammatory drugs and antibiotics alter the risk of breast cancer in women, but roles for bacteria and inflammation in breast malignancies are poorly understood. A recent study in mice suggests that intestinal bacteria can trigger mammary carcinoma. The mechanisms involved in this effect suggest that dysregulate...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-06-3468
更新日期：2007-02-01 00:00:00
abstract：:DNA methyltransferase 1 (DNMT1)-deficient mice are tumor-prone, and this has been proposed to result from the induction of genomic instability. To address whether loss of DNMT1, or the related protein DNMT3b, results in genomic instability in human cancer cells, we used a near-diploid human colorectal cancer cell line...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1961
更新日期：2005-10-01 00:00:00
abstract：:Hematoporphyrin derivative linked by ether bonds (HE) was synthesized by unambiguous procedures in order to compare its properties to hematoporphyrin derivative (HpD). Reverse phase high performance liquid and gel filtration chromatography were used to compare the HE derivatives to HpD. The cellular uptake of HE deriv...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
abstract：:Steroid sulfatase (STS) hydrolyzes several sulfated steroids such as estrone sulfate, dehydroepiandrosterone sulfate, and cholesterol sulfate. In the present study, we have measured STS mRNA levels in 97 breast cancers by reverse transcription-PCR using a fluorescent primer in the presence of an internal standard RNA ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-01-15 00:00:00
abstract：:Rabbit skin was infected with Shope papilloma virus and grafted orthotopically to nude mice. Typical Shope rabbit papillomas developed in most of the grafts, but similarly treated nude mouse skin grafts were not altered. These results demonstrated that xenogeneic tissues retained susceptibility to oncogenic agents aft...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-01-01 00:00:00
abstract：:The presence of a valine (V) versus a phenylanaline (F) at position 158 of Fc gamma RIIIa/CD16a improves the affinity for IgG and is associated with higher therapeutic response to rituximab. Increased CD16 expression on natural killer (NK) cells from donors with the VV or VF versus FF genotype has recently been report...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-6523
更新日期：2008-02-15 00:00:00
abstract：:The process of monoclonal antibody (MAb) binding to tumor cells is greatly influenced by the biology of the respective antigen. This was concluded from an analysis of binding and release of MAbs and MAb fragments to melanoma cells at different concentration levels and different temperatures. With an antigen known to b...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:Our recent allelic analysis of head and neck squamous cell carcinomas identified a high incidence of chromosomal loss on 13q. To further define an area of minimal loss, we tested 60 primary head and neck squamous cell carcinomas in 59 patients for loss of heterozygosity (LOH) by using 10 polymorphic microsatellite mar...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:The ability of osteosarcoma cells to form lung metastases has been inversely correlated to cell surface Fas expression. Downregulation of Fas allows osteosarcoma cells to circumvent FasL-mediated apoptosis upon entrance into the FasL(+) lung microenvironment. However, the mechanism of Fas regulation remains unclear. H...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-1460
更新日期：2012-02-15 00:00:00
abstract：:The expression and activities of epidermal growth factor (EGF) receptor and a highly related protein (Mr approximately 190,000 protein; p190) were characterized from a human glioma cell line, KE. p190 was specifically immunoprecipitated with a monoclonal antibody with specificity against the EGF receptor (Mr approxima...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Monoclonal antibodies (MoAbs) against human osteosarcoma cells were obtained by the fusion of NS/1 mouse myeloma cells with spleen cells from the human osteosarcoma cell line-immunized BALB/c mice. Two hybrid clones were established and designated as 2H10 and 2D3. Both MoAbs reacted strongly with all osteosarcoma tiss...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-04-15 00:00:00
abstract：:We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:Factors affecting the expression of carcinoembryonic antigen (CEA) at the surface of in vitro human colon carcinoma cells were determined using 125I-labeled antibodies. Binding of specific anti-CEA antibodies resulted in polar redistribution of CEA, followed by endocytosis of most of the CEA-anti-CEA complexes. These ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-12-01 00:00:00
abstract：:Statins are inhibitors of cholesterol biosynthesis and protein prenylation that also have been studied in cancer therapy and chemoprevention. With regard to natural killer (NK) cells, only inhibitory effects of statins such as suppression of granule exocytosis have been reported so far. In this study, we show that sta...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1968
更新日期：2010-12-01 00:00:00
