Depleting regulatory T cells with arginine-rich, cell-penetrating, peptide-conjugated morpholino oligomer targeting FOXP3 inhibits regulatory T-cell function.


:CD4+CD25+regulatory T cells (T(reg)) impair anti-tumor and anti-viral immunity. As there are higher T(reg) levels in cancer patients compared with healthy individuals, there is considerable interest in eliminating them or altering their function as part of cancer or viral immunotherapy strategies. The scurfin transcriptional regulator encoded by the member of the forkhead winged helix protein family (FOXP3) is critical for maintaining the functions of T(reg). We hypothesized that targeting FOXP3 expression with a novel arginine-rich, cell-penetrating, peptide-conjugated phosphorodiamidate morpholino (PPMO) based antisense would eliminate T(reg) and enhance the induction of effector T-cell responses. We observed that the PPMO was taken up by activated T cells in vitro and could downregulate FOXP3 expression, which otherwise increases during antigen-specific T-cell activation. Generation of antigen-specific T cells in response to peptide stimulation was enhanced by pre-treatment of peripheral blood mononuclear cells with the FOXP3-targeted PPMO. In summary, modulation of T(reg) levels using the FOXP3 PPMO antisense-based genomic strategy has the potential to optimize immunotherapy strategies in cancer and viral immunotherapy.


Cancer Gene Ther


Cancer gene therapy


Morse MA,Hobeika A,Serra D,Aird K,McKinney M,Aldrich A,Clay T,Mourich D,Lyerly HK,Iversen PL,Devi GR




Has Abstract


2012-01-01 00:00:00














  • Blood outgrowth endothelial cell-based systemic delivery of antiangiogenic gene therapy for solid tumors.

    abstract::Endothelial cells and endothelial cell precursors encoding a therapeutic gene have induced antitumor responses in preclinical models. Culture of peripheral blood provides a rich supply of autologous, highly proliferative endothelial cells, also referred to as blood outgrowth endothelial cells (BOECs). The aim of this ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Bodempudi V,Ohlfest JR,Terai K,Zamora EA,Vogel RI,Gupta K,Hebbel RP,Dudek AZ

    更新日期:2010-12-01 00:00:00

  • Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

    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 ( 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


    authors: Norris JS,Bielawska A,Day T,El-Zawahri A,ElOjeimy S,Hannun Y,Holman D,Hyer M,Landon C,Lowe S,Dong JY,McKillop J,Norris K,Obeid L,Rubinchik S,Tavassoli M,Tomlinson S,Voelkel-Johnson C,Liu X

    更新日期:2006-12-01 00:00:00

  • In vivo manipulation of interleukin-2 expression by a retroviral tetracycline (tet)-regulated system.

    abstract::We have used the tetracycline (tet)-regulated system as described previously to evaluate the applicability of controlled gene expression in cancer gene therapy. As a model gene, we used the human interleukin-2 (IL-2) gene, which has been placed under the transcriptional control of the tetO/promoter. Human melanoma cel...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Pitzer C,Schindowski K,Pomer S,Wirth T,Zöller M

    更新日期:1999-03-01 00:00:00

  • Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand.

    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


    authors: Yu J,Yang K,Zheng J,Zhao W,Sun X

    更新日期:2020-10-13 00:00:00

  • Identification of transcription factors (TFs) and targets involved in the cholangiocarcinoma (CCA) by integrated analysis.

    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


    authors: Yang L,Feng S,Yang Y

    更新日期:2016-12-01 00:00:00

  • Use of monitoring levels of soluble forms of cytokeratin 18 in the urine of patients with superficial bladder cancer following intravesical Ad-IFNα/Syn3 treatment in a phase l study.

    abstract::A phase l study using intravesical Ad-IFNαSyn3 for patients with bacillus Calmette-Guérin-resistant superficial bladder cancer showed a complete remission (CR) of 43% at 90 days after treatment with high levels of interferon-α (IFNα) being produced. Ad-IFNα kills bladder cancer cells by two apoptotic and one necrotic ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Benedict WF,Fisher M,Zhang XQ,Yang Z,Munsell MF,Dinney CN

    更新日期:2014-03-01 00:00:00

  • Oncolytic adenovirus-mediated transfer of the antisense chk2 selectively inhibits tumor growth in vitro and in vivo.

    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


    authors: Chen G,Zhou J,Gao Q,Huang X,Li K,Zhuang L,Huang M,Xu G,Wang S,Lu Y,Ma D

    更新日期:2006-10-01 00:00:00

  • Adenovirus-mediated N5 gene transfer inhibits tumor cell proliferation by induction of apoptosis.

    abstract::Gene therapy designed to initiate apoptotic cell death provides a potentially effective method to treat cancer. A prerequisite for this approach is the identification of genes that function in distinct apoptotic pathways. Although apoptotic pathways initiated by receptors such as tumor necrosis factor receptor-1 are w...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Yin S,Hung MC,Goodrich DW

    更新日期:2000-07-01 00:00:00

  • Endostatin therapy reveals a U-shaped curve for antitumor activity.

    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


    authors: Tjin Tham Sjin RM,Naspinski J,Birsner AE,Li C,Chan R,Lo KM,Gillies S,Zurakowski D,Folkman J,Samulski J,Javaherian K

    更新日期:2006-06-01 00:00:00

  • Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers.

    abstract::Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Barlabé P,Sostoa J,Fajardo CA,Alemany R,Moreno R

    更新日期:2020-05-01 00:00:00

  • Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma.

    abstract::Clear cell renal cell carcinoma (ccRCC) is the highest mortality, invasion, and metastasis subtype of renal cell carcinoma. Bone morphogenetic protein (BMP) family has recently emerged as a group of cancer-related proteins in multiple pathogenesis of cancers. Currently, little is known about the prediction role of BMP...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Xiao W,Wang X,Wang T,Xing J

    更新日期:2020-05-01 00:00:00

  • Therapeutic anti-glioma effect of the combined action of PCSK inhibitor with the anti-tumoral factors secreted by Poly (I:C)-stimulated macrophages.

    abstract::Macrophages plasticity is a key feature in cancer progression. Neoplastic cells can alter their immune functions and orient them into a pro-tumoral phenotype. In this context, we developed a new therapeutic strategy to switch macrophages phenotype and reactivate their anti-tumoral functions. We showed a dual activity ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Rose M,Duhamel M,Aboulouard S,Kobeissy F,Tierny D,Fournier I,Rodet F,Salzet M

    更新日期:2021-01-05 00:00:00

  • Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase.

    abstract::A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 ce...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Li Z,Shanmugam N,Katayose D,Huber B,Srivastava S,Cowan K,Seth P

    更新日期:1997-03-01 00:00:00

  • Virotherapy induces massive infiltration of neutrophils in a subset of tumors defined by a strong endogenous interferon response activity.

    abstract::Oncolytic virotherapy has shown substantial promises as an alternative therapeutic modality for solid tumors in both preclinical studies and clinical trials. The main therapeutic activity of virotherapy derives from the direct lytic effect associated with virus replication and the induction of host immune responses to...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Fu X,Tao L,Rivera A,Xu H,Zhang X

    更新日期:2011-11-01 00:00:00

  • Calcium-sensing receptor antagonist NPS-2143 suppresses proliferation and invasion of gastric cancer cells.

    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


    authors: Zhang ZL,Li ZR,Li JS,Wang SR

    更新日期:2020-08-01 00:00:00

  • Adenovirus-mediated IKKbetaKA expression sensitizes prostate carcinoma cells to TRAIL-induced apoptosis.

    abstract::Despite the fact that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in cancer cells, TRAIL resistance in cancer cells has challenged the use of TRAIL as a therapeutic agent. First, prostate carcinoma cell lines (DU145, LNCaP and PC3) were screened for sensitivity to a...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Sanlioglu AD,Koksal IT,Karacay B,Baykara M,Luleci G,Sanlioglu S

    更新日期:2006-01-01 00:00:00

  • Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors.

    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


    authors: Yaacov B,Eliahoo E,Lazar I,Ben-Shlomo M,Greenbaum I,Panet A,Zakay-Rones Z

    更新日期:2008-12-01 00:00:00

  • Comparison of the E3 and L3 regions for arming oncolytic adenoviruses to achieve a high level of tumor-specific transgene expression.

    abstract::Arming oncolytic adenoviral vectors with anticancer transgenes that can be expressed in a tumor-selective manner may enable the engineering of vectors with increased potency, while retaining their safety profile. Armed oncolytic adenoviral vectors were constructed in which transgene expression has been linked via modi...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Robinson M,Ge Y,Ko D,Yendluri S,Laflamme G,Hawkins L,Jooss K

    更新日期:2008-01-01 00:00:00

  • MicroRNA silencing improves the tumor specificity of adenoviral transgene expression.

    abstract::Adenoviral technology has been thoroughly evaluated for delivering genetic material to tumor tissue and the surrounding microenvironment. Almost any gene can be cloned into an adenovirus (Ad) vector, which when combined with strong, constitutively active promoters permit up to a million-fold amplification of the trans...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Card PB,Hogg RT,Gil Del Alcazar CR,Gerard RD

    更新日期:2012-07-01 00:00:00

  • PiggyBac as a novel vector in cancer gene therapy: current perspective.

    abstract::Selection of suitable delivery system is one of the crucial aspects in gene therapy that determines the efficiency of gene therapy. The past two decades have witnessed extensive efforts for finding safe and efficient vectors to overcome the limitations of viral vectors. The utilization of DNA transposon-based vectors ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Mirzaei H,Sahebkar A,Jaafari MR,Hadjati J,Javanmard SH,Mirzaei HR,Salehi R

    更新日期:2016-02-01 00:00:00

  • Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy.

    abstract::The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposome-coated plasmids carrying the cDNA coding for murine and human angiostatin (CMVang and BSHang) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatm...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Rodolfo M,Catò EM,Soldati S,Ceruti R,Asioli M,Scanziani E,Vezzoni P,Parmiani G,Sacco MG

    更新日期:2001-07-01 00:00:00

  • Decidua mesenchymal stem cells migrated toward mammary tumors in vitro and in vivo affecting tumor growth and tumor development.

    abstract::Mesenchymal stem cells (MSCs) have affinity to tumor sites where they home, affecting their biology and growth. Previously, we have isolated mesenchymal cells from the decidua of the human placenta named as decidua-derived MSCs (DMSCs). The aims of the present study were to investigate the migration capacity of DMSCs ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Vegh I,Grau M,Gracia M,Grande J,de la Torre P,Flores AI

    更新日期:2013-01-01 00:00:00

  • Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral vector inhibits IL-6-dependent proliferation of multiple myeloma cells.

    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


    authors: Yamamoto M,Nishimoto N,Davydova J,Kishimoto T,Curiel DT

    更新日期:2006-02-01 00:00:00

  • Gene therapy of metastatic colon carcinoma: regression of multiple hepatic metastases by adenoviral expression of bacterial cytosine deaminase.

    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


    authors: Block A,Freund CT,Chen SH,Nguyen KP,Finegold M,Windler E,Woo SL

    更新日期:2000-03-01 00:00:00

  • Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3.

    abstract::Aberrantly expressed microRNAs (miRNAs) are involved in breast tumorigenesis. It is still unclear if and how miRNAs-221/222 are implicated in breast cancer and the resistance to estrogen receptor modulator tamoxifen. We investigated the roles and mechanisms of miR-221/222 in breast cancer cells, particularly in modula...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Gan R,Yang Y,Yang X,Zhao L,Lu J,Meng QH

    更新日期:2014-07-01 00:00:00

  • Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy in BT4C rat glioma model.

    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


    authors: Tyynelä K,Sandmair AM,Turunen M,Vanninen R,Vainio P,Kauppinen R,Johansson R,Vapalahti M,Ylä-Herttuala S

    更新日期:2002-11-01 00:00:00

  • Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model.

    abstract::Ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. The present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23H1 expression through adeno-associated virus (AAV)-mediated gene transfer. ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Li J,Zhou J,Chen G,Wang H,Wang S,Xing H,Gao Q,Lu Y,He Y,Ma D

    更新日期:2006-03-01 00:00:00

  • T-bet promotes potent antitumor activity of CD4+ CAR T cells.

    abstract::Chimeric antigen receptor (CAR) therapy has shown promise against B cell malignancies in the clinic. However, limited success in patients with solid tumors has prompted the development of new CAR strategies. In this study, a B7H6-specific CAR was combined with different variants of T-bet, a transcription factor that a...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Gacerez AT,Sentman CL

    更新日期:2018-06-01 00:00:00

  • Molecular conjugate vectors mediate efficient gene transfer into gastrointestinal epithelial cells.

    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


    authors: Batra RK,Berschneider H,Curiel DT

    更新日期:1994-09-01 00:00:00

  • Redirected cellular cytotoxicity by infection of effector cells with a recombinant vaccinia virus encoding a tumor-specific monoclonal antibody.

    abstract::Cytotoxicity is an important function of the immune system that results in the destruction of cellular targets by humoral and/or cellular mechanisms. We wanted to assess the possibility of targeting the lytic function of immune cells toward cancer cells, which express the gene coding for a known tumor antigen (Ag) (GA...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章


    authors: Paul S,Bizouarne N,Dott K,Ruet L,Dufour P,Acres RB,Kieny MP

    更新日期:2000-04-01 00:00:00