Abstract:
BACKGROUND:Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral injection of IFN-gamma retroviral vector in advanced melanoma patients. METHODS:This was a phase I study, in which 13 patients received a single daily injection of a retroviral vector with the IFN-gamma gene for 5 consecutive days (1.5 x 10(8) colony-forming units total dose); patients subsequently underwent resection of the injected lesion to confirm DNA transduction in situ. RESULTS:No toxicity related to the injected vector was observed. Replication competent retrovirus was not observed in any prepared samples (n = 65). IFN-gamma expression was confirmed in 3 of 10 harvested tumor samples; one was equivocal, and DNA transduction was unable to be confirmed by enzyme-linked immunospot assay in six samples. CONCLUSIONS:An injection of IFN-gamma gene/retroviral vector is well tolerated. DNA transduction was demonstrated in human subjects, confirming the feasibility of the direct injection approach for the gene therapy of solid tumors. Further trials to determine optimal schedule and potential efficacy are indicated.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Nemunaitis J,Fong T,Robbins JM,Edelman G,Edwards W,Paulson RS,Bruce J,Ognoskie N,Wynne D,Pike M,Kowal K,Merritt J,Ando Ddoi
10.1038/sj.cgt.7700019subject
Has Abstractpub_date
1999-07-01 00:00:00pages
322-30issue
4eissn
0929-1903issn
1476-5500journal_volume
6pub_type
临床试验,杂志文章abstract::The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the i...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00239-8
更新日期:2020-10-13 00:00:00
abstract::Lung cancer is the most frequently occurring cancer in the world and causes more deaths in the United States than does colon, breast, and prostate cancer combined. Despite advances in treatment modalities including radiation, surgery, and chemotherapy, the overall survival in lung cancer remains low. The cytokine tumo...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700394
更新日期:2001-11-01 00:00:00
abstract::Intratumoral injection of recombinant adenoviral type 5 (Ad5) vectors that carry prodrug-activating enzymes like DT-diaphorase (DTD) could be used to selectively target tumor cells for chemotherapy. To demonstrate the feasibility of this approach, Ad5 vectors were constructed, which express human DTD minigenes for bot...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700430
更新日期:2002-02-01 00:00:00
abstract::p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was c...
journal_title:Cancer gene therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/sj.cgt.7700214
更新日期:2000-07-01 00:00:00
abstract::Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker for the colorectal cancer (CRC). It plays critical roles in the oncogenesis, progression, and metastasis of CRC. DCLK1 can be an intriguing therapeutic target for CRC treatment. However, the molecular mechanism of how DCLK1 functions is unclear currently....
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0144-4
更新日期:2020-09-01 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
更新日期:2013-05-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Cancer gene therapy
pub_type: 已发布勘误
doi:10.1038/s41417-020-0166-y
更新日期:2020-06-01 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::At the Eleventh International Conference on Gene Therapy of Cancer (December 12-14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.cgt.7700602
更新日期:2003-07-01 00:00:00
abstract::Survivin is expressed in most cancers but is undetectable in differentiated adult cells, and plays an important role both in the suppression of apoptosis and mitotic spindle checkpoint; thus it has attracted great interest as a potential drug target. In this study, we investigated the antigene and antiproliferative ef...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700581
更新日期:2003-05-01 00:00:00
abstract::All animal experiments were approved by the Animal Care and Use Committee (ACUC), Louisiana State University Health Science Center and not The People's Hospital of Liaoning Province as indicated in the original version of the Article. The PDF and HTML versions of the Article have been modified accordingly. ...
journal_title:Cancer gene therapy
pub_type: 已发布勘误
doi:10.1038/s41417-019-0082-1
更新日期:2019-07-01 00:00:00
abstract::Bcl-2 is associated with resistance to radiotherapy in prostate cancer. It was recently demonstrated that transduction of LNCaP prostate cells with the PTEN gene resulted in Bcl-2 downregulation. We hypothesized that forced expression of PTEN in prostate cancer cells would sensitize cells to radiation, downregulate Bc...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700673
更新日期:2004-04-01 00:00:00
abstract::The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integr...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.64
更新日期:2016-12-01 00:00:00
abstract::Fusion of the 5' half of the Ewing's sarcoma (ES) gene EWS with the DNA-binding domain of several transcription factors has been detected in many human tumors. The t(11;22)(q24;q12) chromosomal translocation is specifically linked to ES and primitive neuroectodermal tumors and results, in the majority of cases, in the...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700220
更新日期:2000-08-01 00:00:00
abstract::Recurrent or metastatic cancer in most cases remains an incurable disease, and thus alternative treatment strategies, such as oncolytic virotherapy, are of great interest for clinical application. Oncolytic adenoviruses (Ads) have many advantages as virotherapeutic agents and have been safely employed in the clinics. ...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2012.95
更新日期:2013-02-01 00:00:00
abstract::Let-7 miRNAs are involved in carcinogenesis and tumor progression through their roles in maintaining differentiation and normal development. However, there is little research focusing on the effects of let-7 on Wnt-activated self-renewal of breast cancer stem cells. By analyzing the expression levels of let-7 family m...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.3
更新日期:2016-04-01 00:00:00
abstract::Drug metabolizing transgene products, which activate bioreductive cytotoxins, can be used to target treatment-resistant hypoxic tumors. The prodrug AQ4N is bioreduced in hypoxic cells by cytochrome P450s (CYPs) to the cytotoxin AQ4. Previously we have shown that intra-tumoral injection of CYP3A4 and CYP2B6 transgenes ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700933
更新日期:2006-06-01 00:00:00
abstract::We introduced the interleukin-12 (IL-12) gene into mouse renal cell carcinoma (RenCa) cells to develop a tumor vaccine and to examine mechanisms of tumor rejection. IL-12-secreting RenCa (RenCa/IL-12) cells were completely rejected when implanted into syngeneic BALB/c but not athymic nude mice, suggesting that T cells...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700083
更新日期:2000-01-01 00:00:00
abstract::Gene-directed enzyme prodrug therapy (GDEPT) is a promising approach to local management of cancer through targeted chemotherapy. Killing localized tumors by GDEPT in a manner that induces strong antitumor cellular immune responses might improve local management and allow benefit in disseminated cancer. Here we evalua...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700807
更新日期:2005-06-01 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::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::Previous studies have indicated that the cytokine interleukin (IL)-21 may induce both innate and adaptive immune responses against tumors. The goal of this study was to evaluate a new adoptive immunotherapy strategy that combined lymphocytes from mice immunized with a murine myeloma vaccine secreting murine IL-21 (mIL...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.23
更新日期:2010-10-01 00:00:00
abstract::Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2008.31
更新日期:2008-12-01 00:00:00
abstract::As an initial assessment of the feasibility of employing the adenovirus serotype 3 (Ad3) fiber knob as a locale for introducing a tropism-modifying motif, we generated an adenoviral vector containing a six-histidine tag genetically fused to the carboxy-terminus of the Ad3 fiber knob. The heterologous tag proved to be ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700543
更新日期:2003-02-01 00:00:00
abstract::The Ki-ras gene is frequently mutated and/or overexpressed in human cancer. Since it is suspected to play a key role in the pathogenesis of many tumors, there is interest to search for strategies aiming at the specific inhibition of this oncogene. In this paper, we investigated the capacity of a 20 mer G-rich oligonuc...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700722
更新日期:2004-07-01 00:00:00
abstract::NPS-2143 is a calcium-sensing receptor (CaSR) antagonist that has been demonstrated to possess anticancer activity. To date, the effects of NPS-2143 on gastric cancer (GC) cell growth, motility, and apoptosis have not been investigated. In the present study, we firstly investigated the expression of CaSR in GC tissues...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0128-4
更新日期:2020-08-01 00:00:00
abstract::Developing continuous systemic delivery of endostatin has been a goal of many laboratories. We have employed a method of gene therapy utilizing different viral constructs. Here, we report that a new serotype of adeno-associated viruses, which incorporates canine endostatin, provides dose-dependent transgene expression...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700938
更新日期:2006-06-01 00:00:00
abstract::MicroRNAs (miRNAs) are a type of small noncoding RNAs that have a vital role in basic biological processes such as cellular growth, division and apoptosis. A change in the expression of miRNAs can induce many diseases. Recently, the role of miRNA in some of the cancers as a tumor suppressor and oncogene has been recog...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.10
更新日期:2016-07-01 00:00:00
abstract::Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in tumor cells causing direct killing, that is, oncolysis, while sparing normal cells. The oHSVs are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We hypothesized that combining the d...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.75
更新日期:2013-01-01 00:00:00
abstract::Adenovirus (Adv)-mediated herpes simplex virus thymidine kinase (adv/tk) gene therapy combined with ganciclovir (GCV) medication is a promising approach for the treatment of malignant glioma. However, optimal administration and the effect of possible adjuvant treatments have not been fully examined. In the present stu...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700515
更新日期:2002-11-01 00:00:00