Low-Dose Radiation Enhances Survivin-Mediated Virotherapy against Malignant Glioma Stem Cells

Nandi, Sumon; Ulasov, Ilya V.; Tyler, Matthew A.; Sugihara, Adam Quasar; Molinero, Luciana; Han, Yu; Zhu, Zeng B.; Lesniak, Maciej S.

doi:10.1158/0008-5472.can-07-6441

Cited by 80 publications

(68 citation statements)

References 30 publications

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“…[1][2][3][4][5][6] Cancer stem cells (CSCs) mediate tumor metastasis by virtue of their relative resistance to chemotherapy and radiation therapy and contribute to relapse following treatment. 7,8 The inability to target CSCs with current therapies may be a significant factor for treatment failures. Current immunotherapies are primarily directed against tumor differentiation antigens, and thus, preferentially target differentiated cells rather than the CSC population lacking these antigens.…”

Section: Introductionmentioning

confidence: 99%

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

et al. 2015

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Keywords: antitumor immunity, cancer stem cell, dendritic cell, metastasis, vaccine Abbreviations: ALDH, aldehyde dehydrogenase; CSC, cancer stem cell; CSC-DC, CSC lysate-pulsed dendritic cell; DC, dendritic cell; H-DC, heterogeneous, unsorted tumor cell lysate-pulsed dendritic cell; RT, radiation therapy; qRT-PCR, real time quantitative PCR.The inability to target cancer stem cells (CSC) may be a significant factor contributing to treatment failure. We have developed a strategy to target the CSC populations in melanoma and squamous cell carcinoma using CSC lysate-pulsed dendritic cells (DCs). The CSC-DC vaccine was administered in the adjuvant setting after localized radiation therapy of established tumors. Using mouse models we demonstrated that DCs pulsed with CSCs enriched by virtue of their expression of the CSC marker ALDH (termed CSC-DC) significantly inhibited tumor growth, reduced development of pulmonary metastases and prolonged survival. The effect was associated with downregulation of chemokine (C-C motif) receptors CCR7 and CCR10 in tumor cells and decreased expression of the chemokine (C-C motif) ligands CCL21, CCL27 and CCL28 in lung tissue. The CSC-DC vaccine significantly reduced ALDH high CSC frequency in primary tumors. Direct targeting of CSCs was demonstrated by the specific binding of IgG produced by ALDH high CSC-DC vaccineprimed B cells to ALDH high CSCs, resulting in lysis of these target CSCs in the presence of complement. These data suggest that the CSC-DC vaccine approach may be useful in the adjuvant setting where local and systemic relapse are high after conventional treatment of cancers.

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Section: Introductionmentioning

confidence: 99%

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

et al. 2015

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“…Cancer stem cells are relatively resistant to conventional chemotherapy and radiotherapy 1,2 . On the other hand, this population of cells might be the cells responsible for the relapse and progression of cancers after traditional cancer therapies [1][2][3][4] .…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, this population of cells might be the cells responsible for the relapse and progression of cancers after traditional cancer therapies [1][2][3][4] . Due to the lack of expression of differentiated tumor antigens on cancer stem cells, cancer stem cells may escape current immunologic interventions of therapy for cancer, which are mostly designed to target the antigens on the differentiated tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

Lü

Tao

et al. 2014

JoVE

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We identified cancer stem cell (CSC)-enriched populations from murine melanoma D5 syngeneic to C57BL/6 mice and the squamous cancer SCC7 syngeneic to C3H mice using ALDEFLUOR/ALDH as a marker, and tested their immunogenicity using the cell lysate as a source of antigens to pulse dendritic cells (DCs). DCs pulsed with ALDH high CSC lysates induced significantly higher protective antitumor immunity than DCs pulsed with the lysates of unsorted whole tumor cell lysates in both models and in a lung metastasis setting and a s.c. tumor growth setting, respectively. This phenomenon was due to CSC vaccine-induced humoral as well as cellular anti-CSC responses. In particular, splenocytes isolated from the host subjected to CSC-DC vaccine produced significantly higher amount of IFNγ and GM-CSF than splenocytes isolated from the host subjected to unsorted tumor cell lysate pulsed-DC vaccine. These results support the efforts to develop an autologous CSC-based therapeutic vaccine for clinical use in an adjuvant setting.

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“…Radiation-inducible promoters can regulate and control the downstream therapeutic gene expression, a new strategy for radiation-gene therapy founded in recent years [7,8]. It combines traditional radiation treatment with gene therapy, which may reduce radiation dosage and increases efficacy of gene therapy [9,10]. Human tongue squamous cell carcinoma is the most common type of neoplasm in the oral cavity [11,12].…”

Section: Introductionmentioning

confidence: 99%

Radiation-inducible promoter mediated PUMA Gene in the the treatment of Tca8113

Yu¹,

Zhao²,

Luo³

et al. 2011

OJST

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Objective: The aim of this study is to explore the therapeutic effect of the PUMA gene mediated by radiation-inducible promoters in the treatment of tongue squamous cell carcinoma. Methods: Recombinant pcDNA3.1 (+)/E-PUMA was constructed, in which the PUMA gene was mediated by a synthetic radiation inducible promoter. The recombined plasmids were transfected into the Tca8113 cell and xenografts of human tongue squamous carcinoma in naked mice respectively. After 24 h, the tumors were treated with 3 Gy of irradiation to upregulate the PU-MA gene expression. PUMA mRNA was detected by RT-PCR. Proliferating cell nuclear antigen (PCNA) and apoptosis were detected by immunohistochemical method and in situ end-labeling (ISEL) respectively. The data were analyzed using the SPSS11.0 software package for chi-square test. Results: Compared with the control group, the comparative survival rate of Tca8113 cells in the PUMA/IR group was markedly decreased and the xenografts were signifycantly suppressed. Up-regulation of PUMA gene expression was observed in the Tca8113 cells and in the xenografts after irradiation. The apoptosis indices of the Tca-8113 cells and xenograft with irradiation were markedly higher than those without irradiation. At the same time, the proliferation indices of the Tca8113 cells and xenografts with irradiation were markedly lower than those without irradiation. Conclusions: radiation-inducible promoters can serve as molecular switches to improve the expression of PUMA gene in tongue squamous cell carcinoma both in vivo and in vitro. Low-dose induction radiation can significantly improve therapeutic efficiency.

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Low-Dose Radiation Enhances Survivin-Mediated Virotherapy against Malignant Glioma Stem Cells

Cited by 80 publications

References 30 publications

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

Radiation-inducible promoter mediated PUMA Gene in the the treatment of Tca8113

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