Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo.

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, transfer of PSA/CD25 or PSMA cDNA during murine hematopoietic cell differentiation into DCs occurred with approximately 80% efficiency. In vitro, transduced DCs retained allostimulatory function and primed syngeneic T cells for tumor antigen-specific IFN-gamma secretion. In test experiments designed to elucidate mechanisms in vivo, syngeneic recipients of transduced DCs had increased anti-human PSA antibody titers and tumor-specific CD8(+) T cell IFN-gamma secretion with no detectable immune response to CD25. Gene-modified DC recipients had increased protection from specific tumor challenge for at least 18 weeks post-vaccination. DC vaccination also protected both male and female recipients. Gene-modified DC vaccination mediated regression of established, specific gene-expressing, TRAMP-C1 prostate cancer cell tumors. These findings indicate that antibody and cellular responses generated through PSA and PSMA gene transfer into DC yielded protective immunity, thereby providing further preclinical support for the implementation of immuno-gene therapy approaches for prostate cancer.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Medin JA,Liang SB,Hou JW,Kelley LS,Peace DJ,Fowler DH

doi

10.1038/sj.cgt.7700810

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

540-51

issue

6

eissn

0929-1903

issn

1476-5500

pii

7700810

journal_volume

12

pub_type

杂志文章
  • 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

    doi:10.1038/cgt.2016.64

    authors: Yang L,Feng S,Yang Y

    更新日期:2016-12-01 00:00:00

  • Use of targeted cationic liposomes in enhanced DNA delivery to cancer cells.

    abstract::Cationic liposomes are considered to be safe vectors for gene transfer, but they are less efficient at delivering DNA to cells when compared with retroviral vectors. Cationic liposomes complexed with DNA were targeted to specific cells in vitro by means of monoclonal antibodies (mAbs) or ligands associated with the li...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Kao GY,Change LJ,Allen TM

    更新日期:1996-07-01 00:00:00

  • Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population.

    abstract::This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG gro...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2017.13

    authors: Yang HW,Lei P,Xie YC,Han ZL,Li D,Wang SH,Sun ZL

    更新日期:2017-06-01 00:00:00

  • Immunotherapy for murine K1735 melanoma: combinatorial use of recombinant adenovirus expressing CD40L and other immunomodulators.

    abstract::We have constructed and tested five recombinant adenoviruses (Ads) that express a variety of immunomodulators, including CD40 ligand (CD40L), a potent costimulator of several components of the immune system. We demonstrate that CD40L expressed from Ad in K1735 mouse melanoma cells leads to a strong reduction in tumori...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700475

    authors: Peter I,Nawrath M,Kamarashev J,Odermatt B,Mezzacasa A,Hemmi S

    更新日期:2002-07-01 00:00:00

  • A novel gene transfer strategy that combines promoter and transgene activities for improved tumor cell inhibition.

    abstract::Typically, gene transfer strategies utilize a promoter/transgene arrangement that treat these elements independently and do not offer any interplay between them. Our goal was to establish a promoter/transgene combination that would result in improvement in both expression and therapeutic effect by utilizing the transc...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700846

    authors: Strauss BE,Bajgelman MC,Costanzi-Strauss E

    更新日期:2005-12-01 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

    doi:10.1038/sj.cgt.7700021

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

    更新日期:1999-03-01 00:00:00

  • Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses.

    abstract::Oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a variety of cancers. We recently developed MOA5, a tumor-specific midkine promoter-regulated oncolytic vector based on human adenovirus serotype 5 (Ad5). We modified the binding tropism of MOA5 by replacing the cell-binding domain of the ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2014.7

    authors: Takagi-Kimura M,Yamano T,Tagawa M,Kubo S

    更新日期:2014-03-01 00:00:00

  • Human growth hormone gene transfer into tumor cells may improve cancer chemotherapy.

    abstract::Chemotherapy remains the main tool for the treatment of cancers, but is often hampered by tumor cell resistance. In this context, the transfer of genes able to accentuate the effect of anticancer drugs may constitute a useful approach, as exemplified by inactivation of nuclear factor (NF)-kappa B via direct transfer o...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700467

    authors: Cherbonnier C,Déas O,Vassal G,Merlin JL,Haeffner A,Senik A,Charpentier B,Dürrbach A,Bénard J,Hirsch F

    更新日期:2002-06-01 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 (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

    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

  • Inhibitory effects of interferon-gamma plasmid DNA on DMBA-TPA induced mouse skin carcinogenesis.

    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

    authors: Ko JH,Jung BG,Park YS,Lee BJ

    更新日期:2011-09-01 00:00:00

  • Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor rnasin.

    abstract::The growth of new blood vessels is an essential condition for the development of tumors with a diameter greater than 1-2 mm and also for their metastatic dissemination. RNasin, the placental ribonuclease inhibitor, is known to have antiangiogenic activity through the inhibition of angiogenin and basic fibroblast growt...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700302

    authors: Botella-Estrada R,Malet G,Revert F,Dasí F,Crespo A,Sanmartín O,Guillén C,Aliño SF

    更新日期:2001-04-01 00:00:00

  • E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells.

    abstract::Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700739

    authors: Rao XM,Tseng MT,Zheng X,Dong Y,Jamshidi-Parsian A,Thompson TC,Brenner MK,McMasters KM,Zhou HS

    更新日期:2004-09-01 00:00:00

  • Tumor gene therapy by MVA-mediated expression of T-cell-stimulating antibodies.

    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 o...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700461

    authors: Paul S,Regulier E,Rooke R,Stoeckel F,Geist M,Homann H,Balloul JM,Villeval D,Poitevin Y,Kieny MP,Acres RB

    更新日期:2002-05-01 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

    doi:10.1038/cgt.2015.68

    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

  • Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy.

    abstract::Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene gamma(1)34.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in r...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700890

    authors: Jarnagin WR,Zager JS,Hezel M,Stanziale SF,Adusumilli PS,Gonen M,Ebright MI,Culliford A,Gusani NJ,Fong Y

    更新日期:2006-03-01 00:00:00

  • A "combination oligonucleotide" antisense strategy to downregulate thymidylate synthase and decrease tumor cell growth and drug resistance.

    abstract::Thymidylate synthase (TS) catalyzes de novo production of thymidylate for DNA synthesis and cell proliferation. As such, TS has been a target of antitumor chemotherapy for many years. Our laboratory has identified several antisense oligodeoxynucleotides (ODNs) that downregulate TS mRNA and protein, inhibit cell prolif...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700566

    authors: Berg RW,Ferguson PJ,Vincent MD,Koropatnick DJ

    更新日期:2003-04-01 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

    doi:10.1038/s41417-020-00286-1

    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

  • Efficient tumor transduction and antitumor efficacy in experimental human osteosarcoma using retroviral replicating vectors.

    abstract::Retroviral replicating vectors (RRVs) have achieved efficient tumor transduction and enhanced therapeutic benefit in a wide variety of cancer models. Here, we evaluated two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), which utilize different cellular recept...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/s41417-018-0037-y

    authors: Kubo S,Takagi-Kimura M,Kasahara N

    更新日期:2019-02-01 00:00:00

  • The effects of radiation on antitumor efficacy of an oncolytic adenovirus vector in the Syrian hamster model.

    abstract::We report that radiation enhances the antitumor efficacy of the oncolytic adenovirus vector VRX-007 in Syrian hamster tumors. We used tumor-specific irradiation of subcutaneous tumors and compared treatment options of radiation alone or combined with VRX-007 and cyclophosphamide (CP). Radiation therapy further augment...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2013.50

    authors: Young BA,Spencer JF,Ying B,Toth K,Wold WS

    更新日期:2013-09-01 00:00:00

  • Combining CAR T cells and the Bcl-2 family apoptosis inhibitor ABT-737 for treating B-cell malignancy.

    abstract::B-cell malignancies upregulate the B-cell lymphoma 2 (Bcl-2) family inhibitors of the intrinsic apoptosis pathway, making them therapy resistant. However, small-molecule inhibitors of Bcl-2 family members such as ABT-737 restore a functional apoptosis pathway in cancer cells, and its oral analog ABT-263 (Navitoclax) h...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2013.35

    authors: Karlsson H,Lindqvist AC,Fransson M,Paul-Wetterberg G,Nilsson B,Essand M,Nilsson K,Frisk P,Jernberg-Wiklund H,Loskog A

    更新日期:2013-07-01 00:00:00

  • Antitumor immune responses mediated by adenoviral GDEPT using nitroreductase/CB1954 is enhanced by high-level coexpression of heat shock protein 70.

    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

    authors: Djeha HA,Todryk SM,Pelech S,Wrighton CJ,Irvine AS,Mountain A,Lipinski KS

    更新日期:2005-06-01 00:00:00

  • MicroRNA and drug resistance.

    abstract::Chemotherapy is the preferred treatment for malignancies. However, a successful long-term use of chemotherapy is often prevented by the development of drug resistance. Many mechanisms such as gene mutation, DNA methylation and histone modification have important roles in the resistance of cancer cells to chemotherapeu...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/cgt.2010.18

    authors: Ma J,Dong C,Ji C

    更新日期:2010-08-01 00:00:00

  • Manufacture of T cells using the Sleeping Beauty system to enforce expression of a CD19-specific chimeric antigen receptor.

    abstract::T cells can be reprogrammed to redirect specificity to tumor-associated antigens (TAAs) through the enforced expression of chimeric antigen receptors (CARs). The prototypical CAR is a single-chain molecule that docks with TAA expressed on the cell surface and, in contrast to the T-cell receptor complex, recognizes tar...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章,评审

    doi:10.1038/cgt.2014.69

    authors: Singh H,Moyes JS,Huls MH,Cooper LJ

    更新日期:2015-03-01 00:00:00

  • Comparative assessment of TCRBV diversity in T lymphocytes present in blood, metastatic lesions, and DTH sites of two melanoma patients vaccinated with an IL-7 gene-modified autologous tumor cell vaccine.

    abstract::A phase I clinical trial using autologous, IL-7 gene-modified tumor cells in patients with disseminated melanoma has been recently completed. Although no major clinical responses were observed, increased antitumor cytotoxicity was measured in postvaccine peripheral blood lymphocytes in a subset of treated patients. To...

    journal_title:Cancer gene therapy

    pub_type: 临床试验,杂志文章

    doi:10.1038/sj.cgt.7700435

    authors: Carsana M,Tragni G,Nicolini G,Bersani I,Parmiani G,Anichini A,Sun YS,Möller P,Schadendorf D,Sensi ML

    更新日期:2002-03-01 00:00:00

  • Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

    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

    authors: Dummer R,Bergh J,Karlsson Y,Horowitz JA,Mulder NH,Huinink DTB,Burg G,Hofbauer G,Osanto S

    更新日期:2000-07-01 00:00:00

  • Does preventive vaccination with engineered tumor cells work in cancer-prone transgenic mice?

    abstract::The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice ...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:

    authors: Morel A,de La Coste A,Fernandez N,Berson A,Kaybanda M,Molina T,Briand P,Haddada H,Guillet JG,Antoine B,Viguier M,Kahn A

    更新日期:1998-03-01 00:00:00

  • Mining the adenovirus virome for oncolytics against multiple solid tumor types.

    abstract::Although there are 55 serotypes of adenovirus (Ad) that infect humans, Ad serotype 5 (Ad5) is the most widely studied because of the availability of commercial kits for its genetic manipulation. In fact, engineered Ad 5 is currently being used in all of the 87 global clinical trials utilizing Ad for the treatment of c...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2011.47

    authors: Chen CY,Weaver EA,Khare R,May SM,Barry MA

    更新日期:2011-10-01 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

    doi:10.1038/sj.cgt.7700877

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

    更新日期:2006-01-01 00:00:00

  • Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study.

    abstract::Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/cgt.2010.4

    authors: García-Castro J,Alemany R,Cascalló M,Martínez-Quintanilla J,Arriero Mdel M,Lassaletta A,Madero L,Ramírez M

    更新日期:2010-07-01 00:00:00

  • Targeting gene expression to tumor cells with loss of wild-type p53 function.

    abstract::The tumor suppressor protein p53 is a transcription factor that can positively regulate the expression of critical target genes involved in negative control of cell growth or induction of apoptosis; p53 is also able to suppress the transcription of other genes by virtue of its ability to bind components of the basal t...

    journal_title:Cancer gene therapy

    pub_type: 杂志文章

    doi:10.1038/sj.cgt.7700091

    authors: Zhu J,Gao B,Zhao J,Balmain A

    更新日期:2000-01-01 00:00:00