Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism

Cheng, Wen-Fang; Mc, Chang; Sun, Wei‐Zen; Lee, Chien‐Nan; Lin, Hui‐Yi; Yn, Su; Cy, Hsieh; Ca, Chen

doi:10.1038/gt.2008.25

Cited by 23 publications

(28 citation statements)

References 44 publications

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“…19 The death of cells expressing plasmid DNA would decrease the observed luciferase activity. Co-administration of DNA encoding anti-apoptotic proteins [28][29][30] may avoid this cell death and further enhance the effect of OSU-HDAC42 on the induction of CMV promoter-controlled gene expression.…”

Section: Discussionmentioning

confidence: 99%

An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine

Lai

et al. 2009

Cancer Gene Ther

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The cytomegalovirus (CMV) promoter is considered to be one of the strongest promoters for driving the in vivo expression of genes encoded by DNA vaccines. However, the efficacy of DNA vaccines has so far been disappointing (particularly in humans), and this might be explained in part by histone deacetylase (HDAC)-mediated chromatin condensation. Hence, we sought to investigate whether increasing the expression of DNA vaccine antigens with the HDAC inhibitor OSU-HDAC42 would enhance the efficacy of DNA vaccines in vivo. A luciferase assay was used to determine the effects of OSU-HDAC42 on CMV promoter-driven DNA plasmids in vitro and in vivo. Three HDAC inhibitors were able to activate expression from the CMV promoter in NIH3T3 cells and MBT-2 bladder cancer cells. The expression of luciferase was significantly enhanced by co-administration of pCMV-luciferase and OSU-HDAC42 in mice. To explore whether OSU-HDAC42 could enhance the specific antitumor activity of a neu DNA vaccine driven by the CMV promoter, we evaluated therapeutic effects and immune responses in a mouse tumor natively overexpressing HER2/neu. Mice receiving OSU-HDAC42 in combination with the CMV-promoter neu DNA vaccine exhibited stronger antitumor effects than mice given the DNA vaccine only. In addition, a correlation between the antitumor effects and the specific cellular immune responses was observed in the mice receiving the DNA vaccine and OSU-HDAC42.

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Section: Discussionmentioning

confidence: 99%

An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine

Lai

et al. 2009

Cancer Gene Ther

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“…We hypothesize that gold particle-coated DNA vaccination may induce non-specific immune responses to enhance the antigen-specific immune responses by the local burning effect on the bombarded skin, as shown in our earlier studies. 19,51 Another possible mechanism is that the gold beads alone can upregulate the antigenpresenting cells, 36 and these upregulated DCs can induce more potent antigen-specific immune responses when encountering specific antigens.…”

Section: Discussionmentioning

confidence: 99%

“…For the detection of HPV 16 E7-specific antibodies in sera, direct ELISA was used as described previously. 51,52 Briefly, a 96-microwell plate was coated with 100 ml of bacteria-derived HPV-16 E7 proteins (0.5 mg ml…”

Section: Intracellular Cytokine Staining and Flow Cytometry Analysismentioning

confidence: 99%

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects

Sun

et al. 2009

Gene Ther

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Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8 + T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.

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“…Growing evidence suggests TAM promote tumor growth and progression, instead of fighting against tumor as considered previously [24]. In certain instance such as hypoxia, the TAM polarizes to a type 2 macrophage (M2)-like type [25]. M2-like TAM exerts a profound immunosuppressive effect by secreting and releasing cytokine such as CCL17, CCL22 or CCL24.…”

Section: Components Of Cancer Microenvironmentmentioning

confidence: 99%

“…Researchers took advantage of the pro-survival attributes of CTGF and constructed a fusion DNA vaccine which was composed of CTGF and a model tumor antigen E7 [25]. The CTGF/E7 vaccine prolonged the survival of dendritic cells in vivo and thus enhanced the CD4+ and CD8+ T cells response.…”

Section: Vaccines Targeting Fibroblast In the Microenvironmentmentioning

confidence: 99%

Cancer Microenvironment and Cancer Vaccine

Ding¹,

Zou²,

Wei³

2012

Cancer Microenvironment

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The cancer microenvironment is constituted of non-transformed host stromal cells such as endothelial cells, fibroblasts, various immune cells, and a complex extracellular matrix secreted by both the normal and neoplastic cells embedded in it. The importance of the microenvironment and its potential in cancer therapy is just being established. Among modalities that target the microenvironment, cancer vaccine is a unique strategy which is aimed to elicit specific immunity against components in the microenvironment. Most, if not all, components can be targeted by the vaccines. The most extensively studied are the endothelial cells, fibroblasts and macrophages as well as ECM. Vaccines are in development for each of them. All the vaccines were proved to be effective at providing protective or therapeutic anti-tumor effects in the pre-clinical models. A few of them have been tested in the clinical trials. The mechanisms of the vaccines were mainly related to the cellular immune response such as CD8+ cytotoxic T cells, and in some instances CD4+ Th cells were involved as well. The present review also discussed the hurdles associated with the microenvironment-based vaccines such as the selection of suitable patients with appropriate biomarkers. With the rapid increase of our knowledge in the cancer microenvironment, the proof-of-concept of microenvironment-based cancer vaccines will surely expand our armamentarium against cancer.

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Connective tissue growth factor linked to the E7 tumor antigen generates potent antitumor immune responses mediated by an antiapoptotic mechanism

Cited by 23 publications

References 44 publications

An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine

An HDAC inhibitor enhances the antitumor activity of a CMV promoter-driven DNA vaccine

Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects

Cancer Microenvironment and Cancer Vaccine

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