Induction of anti‐tumour immunity by dendritic cells transduced with hTERT recombinant adenovirus in mice

Chen, Ling; Tang, Xu-Dong; Yu, Songtao; Ai, Zhihua; Fang, Dian‐Chun; Cai, Yulong; Luo, Yang; Liang, Guangping; Yang, Shi‐Ming

doi:10.1002/path.2493

Cited by 16 publications

(17 citation statements)

References 28 publications

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“…16 Furthermore, the transduction of dendritic cells with recombinant-adenovirus hTERT induced hTERT-specific cytotoxic T lymphocytes in vitro and in vivo . 17, 18 During a previous study, we showed that hTERT promoted the invasion of telomerase-negative tumor cells in vitro . 19 Moreover, we also demonstrated that hTERT RNAi overcame the resistance of HCC cells to TRAIL via the mitochondrial type II apoptosis pathway and a telomerase-dependent pathway.…”

Section: Discussionmentioning

confidence: 98%

miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase

et al. 2014

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hTERT is the catalytic subunit of the telomerase complex. Elevated expression of hTERT is associated with the expansion and metastasis of gastric tumor. In this study, we aimed to identify novel tumor suppressor miRNAs that restrain hTERT expression. We began our screen for hTERT-targeting miRNAs with a miRNA microarray. miRNA candidates were further filtered by bioinformatic analysis, general expression pattern in different cell lines, gain-of-function effects on hTERT protein and the potential of these effects to suppress hTERT 3′ untranslated region (3′UTR) luciferase activity. The clinical relevance of two miRNAs (miR-1207-5p and miR-1266) was evaluated by real-time RT-PCR. The effects of these miRNAs on cell growth, cell cycle and invasion of gastric cancer cells were measured with CCK-8, flow cytometry and transwell assays. Finally, the ability of these miRNAs to suppress the transplanted tumors was also investigated. Fourteen miRNAs were identified using a combination of bioinformatics and miRNA microarray analysis. Of these fourteen miRNAs, nine were expressed at significantly lower levels in hTERT-positive cell lines compared with hTERT-negative cell lines and five could downregulate hTERT protein expression. Only miR-1207-5p and miR-1266 interacted with the 3′ UTR of hTERT and the expression levels of these two miRNAs were significantly decreased in gastric cancer tissues. These two miRNAs also inhibited gastric tumor growth in vitro and in vivo. Altogether, miR-1207-5p and miR-1266 were determined to be hTERT suppressors in gastric cancer, and the delivery of these two miRNAs represents a novel therapeutic strategy for gastric cancer treatment.

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Section: Discussionmentioning

confidence: 98%

miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase

et al. 2014

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“…However, heterogeneous expression of most of the characterized tumor antigens limits the broad applicability of cancer vaccines that target such antigens (25,26). Therefore, it is necessary for clinicians to identify universal TAAs for immunotherapy of different types of tumors.…”

Section: Discussionmentioning

confidence: 99%

Multiple Antigenic Peptides of Human Heparanase Elicit a Much More Potent Immune Response against Tumors

Wang

Tang

Lü

et al. 2011

Cancer Prevention Research

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Peptide vaccination for cancer immunotherapy requires an ideal immune response induced by epitope peptides derived from tumor-associated antigens (TAA). Heparanase is broadly expressed in various advanced tumors. Accumulating evidence suggests that heparanase can serve as a universal TAA for tumor immunotherapy. However, due to the low immunogenicity of peptide vaccines, an ideal immune response against tumors usually cannot be elicited in patients. To increase the immunogenicity of peptide vaccines, we designed three 4-branched multiple antigenic peptides (MAP) on the basis of the human leukocyte antigen (HLA)-A2-restricted cytotoxic T lymphocyte (CTL) epitopes of human heparanase that we identified previously as antigen carriers. Our results show that MAP vaccines based on the HLA-A2-restricted CLT epitopes of human heparanase were capable of inducing HLA-A2-restricted and heparanasespecific CTL in vitro and in mice. Moreover, compared with their corresponding linear peptides, heparanase MAP vaccines elicited much stronger lysis of tumor cells by activating CD8þ T lymphocytes and increasing the releasing of IFN-g. However, these heparanase-specific CTLs did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirm the safety of these MAP vaccines. Therefore, our findings indicate that MAP vaccines based on CTL epitopes of human heparanase can be used as potent immunogens for tumor immunotherapy because of advantages such as broad spectrum, high effectiveness, high specificity, and safety. Cancer Prev Res; 4(8); 1285-95. Ó2011 AACR.

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“…Because RNA-based vaccines have many advantages including easily preparation, low price, specificity, control, and no risk of incorporation into the host genome [61]. DCs were transfected with tumor mRNA encoding TAA or epitopes by using carriers [61, 62] or electroporation [63, 64]. This can also induce tumor-specific immunity in vitro .…”

Section: Methods Used In Genetically Engineered Dcsmentioning

confidence: 99%

Gene Carriers and Transfection Systems Used in the Recombination of Dendritic Cells for Effective Cancer Immunotherapy

Chen

Yao

Tabata

et al. 2010

Journal of Immunology Research

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Dendritic cells (DCs) are the most potent antigen-presenting cells. They play a vital role in the initiation of immune response by presenting antigens to T cells and followed by induction of T-cell response. Reported research in animal studies indicated that vaccine immunity could be a promising alternative therapy for cancer patients. However, broad clinical utility has not been achieved yet, owing to the low transfection efficiency of DCs. Therefore, it is essential to improve the transfection efficiency of DC-based vaccination in immunotherapy. In several studies, DCs were genetically engineered by tumor-associated antigens or by immune molecules such as costimulatory molecules, cytokines, and chemokines. Encouraging results have been achieved in cancer treatment using various animal models. This paper describes the recent progress in gene delivery systems including viral vectors and nonviral carriers for DC-based genetically engineered vaccines. The reverse and three-dimensional transfection systems developed in DCs are also discussed.

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Induction of anti‐tumour immunity by dendritic cells transduced with hTERT recombinant adenovirus in mice

Cited by 16 publications

References 28 publications

miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase

miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase

Multiple Antigenic Peptides of Human Heparanase Elicit a Much More Potent Immune Response against Tumors

Gene Carriers and Transfection Systems Used in the Recombination of Dendritic Cells for Effective Cancer Immunotherapy

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