In vitro generation of cytotoxic and regulatory T cells by fusions of human dendritic cells and hepatocellular carcinoma cells

Koido, Shigeo; Homma, Sadamu; Hara, Eiichi; Mitsunaga, Makoto; Namiki, Yoshihisa; Takahara, Akitaka; Nagasaki, Eijiro; Komita, Hideo; Sagawa, Yukiko; Ohkusa, Toshifumi; Fujise, Kiyotaka; Gong, Jianlin; Tajiri, Hisao

doi:10.1186/1479-5876-6-51

Cited by 21 publications

(33 citation statements)

References 62 publications

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“…IL-2 is capable of inducing a distinct CTL effector function (25) and the administration of adenovirus vector-encoding mouse IL-2 (AdmIL-2) may augment the antitumor effect of TRAIL on tumors in mice (26). Activated T cells are able to produce IFN-γ and induce cytolysis of autologous tumor or semi-allogeneic targets by an MHC class I-restricted mechanism (27). DCs transduced with the recombinant adenovirus-encoding peptide may effectively induce antigen-specific T cell proliferation, augment the number of IFN-γ-secreting T-cells and induce antigen-specific CTLs capable of lysing target cells pulsed with the peptide (28,29).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of hepatocellular carcinoma growth by adenovirus-mediated expression of human telomerase reverse transcriptase COOH-27 terminal polypeptide in mice

Gong

et al. 2013

Oncology Letters

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A 27-kDa C-terminal fragment of human telomerase reverse transcriptase, hTERTC27, has previously been reported to inhibit the growth and tumorigenicity of HeLa human cervical cancer cells and U87-MG human glioblastoma multiforme cells. However, the antitumor effects of hTERTC27 in hepatoma and its underlying mechanisms are unclear. In the current study, the therapeutic effect of hTERTC27, mediated by recombinant adenovirus, in hepatocellular carcinoma (HCC) was explored in vitro and in vivo to investigate the possible mechanisms. The results indicated that recombinant adenovirus carrying hTERTC27 (rAdv-hTERTC27) effectively inhibited the growth and induced apoptosis of the Hepa 1–6 HCC cells. Dendritic cells transduced with rAdv-hTERTC27 were highly effective at inducing antigen-specific T cell proliferation and increasing the activated cytotoxicity of T cells against Hepa 1–6 cells. HCC was inhibited significantly when a single dose of 5×107 pfu rAdv-hTERTC27 was administered intravenously. In summary, the results of this study demonstrated that rAdv-hTERTC27 may serve as a reagent for intravenous administration when combined with telomerase-based gene therapy and immunotherapy for cancer.

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Section: Discussionmentioning

confidence: 99%

Inhibition of hepatocellular carcinoma growth by adenovirus-mediated expression of human telomerase reverse transcriptase COOH-27 terminal polypeptide in mice

Gong

et al. 2013

Oncology Letters

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“…More importantly, in preclinical studies the fusions were also effective to induce CTL responses in vitro using colorectal [25, 97–102], gastric [103, 104], pancreatic [105], breast [43, 106–110], laryngeal [111], ovarian [34, 44, 112], lung [113], prostate [114, 115], renal [116, 117], and hepatocellular [118–120] carcinoma, leukemia [121–126], myeloma [127, 128] sarcoma [129, 130], melanoma [29, 131–133], glioma [124], and plasmacytoma [134]. …”

Section: Tumor/dc Fusions Vaccinementioning

confidence: 99%

Regulation of Tumor Immunity by Tumor/Dendritic Cell Fusions

Koido

Homma

Hara

et al. 2010

Journal of Immunology Research

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The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment.

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“…Treatment of cancer patients with DC/tumour fusion cells alone may be limited by the induction of immunosuppressive mechanisms. DC/tumour fusion cells can induce not only antigen-specific CTLs but also Tregs, which may counteract their therapeutic effects [49]. Some chemotherapeutic agents, such as cyclophosphamide and gemcitabine, can activate anti-tumour immunity by depleting Tregs and myeloid-derived suppresser cells (MDSCs) [50], leading to improved clinical outcomes.…”

Section: Future Cancer Regimens Using Dc/tumour Fusion Cellsmentioning

confidence: 99%