Translation of the radio- and chemo-inducible TNFerade vector to the treatment of human cancers

Weichselbaum, Ralph R.; Küfe, Donald

doi:10.1038/cgt.2009.37

Cited by 37 publications

(26 citation statements)

References 78 publications

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“…Preclinical studies have shown that radiation combined with TNFerade TM vector administration was associated with a 5-fold increase in TNF-␣ levels and a delay in tumor growth compared with tumors treated with vector alone. Similar results have been obtained in studies combining TNFerade TM with chemotherapeutic agents [13,14] . TNFerade TM has been combined with radiotherapy in patients with advanced solid tumors and sarcoma and with chemoradiotherapy in patients with locally advanced pancreatic cancer [15][16][17] .…”

supporting

confidence: 86%

A Pilot Feasibility Study of TNFerade™ Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer

et al. 2010

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Objective: The purpose of this pilot study was to evaluate the feasibility and tolerability of weekly intratumoral TNFerade™ injections combined with concurrent capecitabine and radiotherapy in the treatment of patients with locally advanced rectal cancer. Methods: Patients with T3, T4, or N+ rectal cancer received radiotherapy to a total dose of 50.4–54 Gy in combination with capecitabine 937.5 mg/m2 p.o. b.i.d. TNFerade™ at a dose of 4 × 1010 particle units was injected into the rectal tumor on the first day of radiotherapy and weekly for a total of 5 injections. Surgery was performed 5–10 weeks after the completion of chemoradiation. Results: Nine patients were enrolled in this pilot trial. The stage was cT2 in 2 patients, cT3 in 6 patients, cT4 in 1 patient, N– in 7 patients and N+ in 2 patients. Eight patients completed all treatments. Grade 3 hematologic toxicity was observed in 2 patients. There was no toxicity directly attributable to the injection procedure. A complete pathologic response was observed in 2 of 9 patients. Conclusions: This study demonstrates the feasibility of weekly intratumoral TNFerade™ injections during chemoradiotherapy for locally advanced rectal cancer. Pathologic responses with this combination compare favorably to published rates.

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confidence: 86%

A Pilot Feasibility Study of TNFerade™ Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer

et al. 2010

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“…To minimize systemic toxicity, TNFα has been engineered into an adenoviral vector with expression controlled by a radiation-responsive promoter (reviewed in 167 ). This promoter has been optimized to generate up to a 3-fold induction of gene expression following radiation therapy 168 and this construct has been successfully used to induce vascular thrombosis in human tumor xenografts in immunodeficient mice 169 .…”

Section: Introductionmentioning

confidence: 99%

Stimulating Innate Immunity to Enhance Radiation Therapy–Induced Tumor Control

Baird

Monjazeb

Shah

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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Novel ligands that target Toll-like receptors and other innate recognition pathways represent a potent strategy for modulating innate immunity to generate anti-tumor immunity. While many of the current clinically successful immunotherapies target adaptive T-cell responses, both pre-clinical and clinical studies suggest that adjuvants have the potential to enhance the scope and efficacy of cancer immunotherapy. Radiation may be a particularly good partner to combine with innate immune therapies, since it is a highly efficient means to kill cancer cells, but may fail to send the appropriate inflammatory signals needed to act as an efficient endogenous vaccine. This may explain why although radiation therapy is a highly used cancer treatment, true abscopal effects – regression of disease outside the field without additional systemic therapy – are extremely rare. This review focuses on efforts to combine innate immune stimuli as adjuvants with radiation, creating a distinct and complementary approach from T cell targeted therapies to enhance anti-tumor immunity.

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“…By targeting those important oncogenes and others relative genes, this strategy efficiently showed some amazing results [29][30][31]. In our study, we applied plasmid-based RNAi to knockdown gene expression.…”

Section: Discussionmentioning

confidence: 92%

Enhanced radiosensitivity of EC109 cells by inhibition of HDAC1 expression

2010

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Histone deacetylase (HDAC) activity plays the role of deacetylation of histone and non-histone proteins, which can alter gene expression patterns and cell behavior potentially associated with malignant transformation. Aberrant expression of HDAC1 has been found in various types of cancers, which indicated that it might be a target for cancer therapy. In this study, overexpression of HDAC1 was found in esophageal cancer samples by real-time RT-PCR, compared with adjacent non-cancerous tissues. To further verify the possibility of anticancer treatment by silencing the increased HDAC1 in esophageal carcinoma cells, HDAC1 expression was knockdown using plasmid-based RNA interference (RNAi). Results showed the HDAC1 expression was efficiently inhibited and the acetylation of histone H3 was significantly increased by RNAi in EC109 cells. Increased apoptotic cell death was observed when HDAC1 expression was knockdown, which indicated that cells were more sensitive to radiation. Moreover, the results also showed DNA was more easily broken by radiation in EC109 cells when HDAC1 expression was knockdown, as measured by γH2AX foci and single-cell electrophoresis. Our data suggested that targeting the increased HDAC1 expression might be feasible for esophageal cancer therapy.

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Translation of the radio- and chemo-inducible TNFerade vector to the treatment of human cancers

Cited by 37 publications

References 78 publications

A Pilot Feasibility Study of TNFerade™ Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer

A Pilot Feasibility Study of TNFerade™ Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer

Stimulating Innate Immunity to Enhance Radiation Therapy–Induced Tumor Control

Enhanced radiosensitivity of EC109 cells by inhibition of HDAC1 expression

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