Gene therapy progress and prospects cancer: oncolytic viruses

Liu, Ta‐Chiang; Kirn, David H.

doi:10.1038/gt.2008.72

Cited by 145 publications

(130 citation statements)

References 60 publications

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“…Previous reports have shown the therapeutic potentials in other tumors. In clinic, a multicenter randomized phase 3 clinical trial showed that the combination therapy with H101 for head and neck squamous cell carcinoma and esophageal cancer yielded a 27% increase in overall response rates compared with fluorouracil plus cisplatin-based chemotherapy alone (22). This virus was approved by the Chinese State Food and Drug Administration for the treatment of late-stage refractory nasopharyngeal cancer.…”

Section: Discussionmentioning

confidence: 99%

“…A variety of viruses have shown oncolytic properties including adenovirus, herpes simplex virus, Newcastle disease virus, vesicular stomatitis virus and reovirus (22). Among a variety of oncolytic viral agents, CRAds specifically aimed at killing tumor cells while sparing normal cells have been developed as new agents for cancer therapy (23,24), and demonstrated efficacy and safety in preclinical (25,26) and clinical trials (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

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The antitumor effects of oncolytic adenovirus H101 against lung cancer

Lei

Yang

et al. 2015

International Journal of Oncology

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Abstract. Lung cancer is the leading cause of cancer mortality in both men and women, with dismal survival rates due to latestage diagnoses and a lack of efficacious therapies. The new treatment options with completely novel mechanism of therapeutic activity are needed for lung cancer to improve patient outcome. The present study was aimed at testing the efficacy of recombinant adenovirus H101 as an oncolytic agent for killing human lung cancer cell lines in vitro and in vivo. We assessed the coxsackievirus adenovirus receptor (CAR) expression on human lung cancer cell lines by RT-PCR and immunocytochemistry staining. Viral infectivity and viral replication in lung cancer cells was assayed by flow cytometry and real-time fluorescent quantitative PCR. After H101 treatment, cytotoxic effect, cell cycle progression and apoptosis were further examined by lactate dehydrogenase release assay and flow cytometry in vitro, respectively. In vivo, antitumor effects of H101 were assessed on SCID Beige mice xenografted with human lung cancer cells. Receptor characterization confirmed that human lung cancer cell lines expressed CAR receptor for adenovirus type 5. Lung cancer cells were sensitive to infection by the H101 virus. H101 infection and replication resulted in very potent cytotoxicity, G2/M phase arrest and cell lysis. In vivo, we also showed that H101 significantly inhibited tumor growth following intratumoral injection, with virus replication, cell degeneration and necrosis in the tumor tissue. These results have important implications for the treatment of human lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The antitumor effects of oncolytic adenovirus H101 against lung cancer

Lei

Yang

et al. 2015

International Journal of Oncology

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“…Oncolytic viruses displaying various mechanisms of action have been developed over the past 15 years. These include viral mutants, in which genes critical for viral growth in normal cells but not in tumor cells were deleted, pseudotyped viruses, in which normal viral tropism was ablated, and engineered viruses binding to specific surface receptors that are expressed exclusively/preferentially on tumor cells (Alemany et al, 2000;Khuri et al, 2000;Kirn, 2000;Fukuhara et al, 2005Fukuhara et al, , 2009Kasuya et al, 2005;Liu and Kirn, 2008;Dorer and Nettelbeck, 2009). Interestingly, oncolytic viruses can kill apoptosis-resistant tumor cells, and do not show cross-resistance with existing therapies.…”

Section: Strategies To Selectively Kill Tumor Cellsmentioning

confidence: 99%

Towards novel paradigms for cancer therapy

et al. 2010

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Cancer is a complex progressive multistep disorder that results from the accumulation of genetic and epigenetic abnormalities, which lead to the transformation of normal cells into malignant derivatives. Despite enormous progress in the understanding of cancer biology including the decryption of multiple regulatory networks governing cell growth and death, and despite the possibility of analyzing (epi)genetic deregulation at the genome-wide scale, cancertargeted therapy is still the exception. In fact, to date there are still far too few examples of therapies leading to cure; treatment-derived toxicity is a major issue, and cancer remains to be one of the largest causes of death worldwide. The purpose of this review is to discuss the state of the art of cancer therapy with respect to the key issue of any treatment, namely its target selectivity. Therefore, we recapitulate and discuss current concepts and therapies targeting tumorspecific features, including oncofusion proteins, aberrant kinase activities and epigenetic tumor makeup. We analyze strategies designed to induce tumor-selective death such as the use of oncolytic virus, tumoricidal proteins (NS1, Eorf4, apoptin, HAMLET (human a-lactalbumin made lethal to tumor cells)) and activation of signaling pathways involved in tumor surveillance. We emphasize the potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway, an essential component of the evolutionary developed defense systems that eradicate malignant cells. Finally, we discuss the necessity of targeting tumor-initiating cells (TICs) to avoid relapse and increase the chances of complete remission, and describe emerging concepts that might provide novel avenues for cancer therapy.

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“…5,6 However, limited therapeutic effect has been reported and further development of Onyx-015 was abandoned in the United States. 7 The rights of Onyx-015 were bought by a Chinese company, Sunway Biotech, which has completed phase III clinical studies with H101, an Ad structurally similar to Onyx-015. 2 The company reported a 79% positive response rate for H101 plus chemotherapy as compared with 40% for chemotherapy alone in clinical trials performed on Chinese cancer patients.…”

Section: Introductionmentioning

confidence: 99%