Radiation Therapy Potentiates Effective Oncolytic Viral Therapy in the Treatment of Lung Cancer

Adusumilli, Prasad S.; Stiles, Brendon M.; Chan, M; Chou, Ting‐Chao; Wong, Richard J.; Rusch, Valerie W.; Fong, Yuman

doi:10.1016/j.athoracsur.2005.01.048

Cited by 49 publications

(37 citation statements)

References 23 publications

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“…We and others have previously shown that IR increased oncolytic HSV-1 replication. [11][12][13][14][15][16][17][18][19][20][21][22][23] The hypothesis tested in this series of experiments was that if varying the timing of IR in relation to the timing of viral injection would result in a further enhancement of viral replication.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16][17][18][19][20][21][22][23] Specifically, g 1 34.5 deleted HSV-1 combined with IR resulted in increased viral replication and glioma-xenograft regression in hindlimb and orthotopic preclinical murine glioma models. 11,17 Mechanistic studies have elucidated multiple pathways through which IR enhances viral replication.…”

Section: Introductionmentioning

confidence: 99%

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Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

et al. 2011

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Oncolytic viruses have been combined with standard cancer therapies to increase therapeutic efficacy. Given the sequential activation of herpes viral genes (herpes simplex virus-1, HSV-1) and the temporal cellular changes induced by ionizing radiation, we hypothesized an optimal temporal sequence existed in combining oncolytic HSV-1 with ionizing radiation. Murine U-87 glioma xenografts were injected with luciferase encoding HSV-1, and ionizing radiation (IR) was given at times before or after viral injection. HSV-1 replication and tumor-volume response were followed. Radiation given 6-9 h after HSV-1 injection resulted in maximal viral luciferase expression and infectious viral production in tumor xenografts. The greatest xenograft regression was also seen with radiation given 6 h after viral injection. We then tested if HSV-1 replication had a dose response to ionizing radiation. HSV-1 luciferase expression exhibited a dose response as xenografts were irradiated from 0 to 5 Gy. There was no difference in viral luciferase expression as IR dose increased from 5 Gy up to 20 Gy. These results suggest that the interaction of IR with the HSV-1 lytic cycle can be manipulated for therapeutic gain by delivering IR at a specific time within viral replicative cycle.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

et al. 2011

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“…15,16 Recent researches to improve the clinical outcome in such patients include altered irradiation fraction schedule and the introduction of chemotherapy, biotherapy, immunotherapy, virotherapy, or gene therapy on a concurrent or adjuvant basis. [17][18][19][20][21][22] Survivin gene expression has been identified in a majority of NSCLC. 3 Additionally, Tamm et al 23 reported that among all the human tumor cells screened, lung cancer cells expressed the highest levels of survivin.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells

Yang

Weng

et al. 2009

Cancer Gene Ther

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Expression of survivin has been reported to be correlated with shorter survival in patients with non-small cell lung cancer (NSCLC), and overexpression of survivin may lead to radioresistance in various human cancers. In this study, we inhibited survivin expression by using an adenoviral vector (AdsiSurvivin)-mediated RNA interference to elucidate the combined effect of survivin-targeting gene therapy and radiotherapy on the NSCLC cells. Our data showed that AdsiSurvivin exerted survivin gene silencing, induced apoptosis, and significantly attenuated the growth potential in NSCLC cells within 72 h after infection. The combined treatment modalities with AdsiSurvivin infection and radiation were significantly more potent on cell-growth inhibition than monotherapy. In H1650, H460, A549, and H1975 human NSCLC cells, the survival ratios of AdsiSurvivin-treated groups at multiplicity of infection of 25 and 50 were significantly lower than those of control groups at varying radiation dose (0-8 Gy; three-way analysis of variance, Po0.05). The cytotoxicity of combined AdsiSurvivin infection and irradiation increased in a dose-dependent manner in both the virus and the irradiation treatment. Knockdown of the survivin gene expression seems to be a promising treatment strategy for NSCLC. Our data warrant the need for further effort to develop survivin-targeted radiosensitizer for lung cancer treatment.

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“…Therefore, upregulation of GADD34 expression complements and substitutes for 34.5 gene, leading to increased viral protein synthesis and viral replication [61]. The upregulation of GADD34 expression by radiation in tumor cell infected with HSV was seen in head-and-neck cancer, cholangiocarcinoma and lung cancer [62][63][64]. It is also reported that enhanced expression of host cellular ribonucleotide reductase (RR) following radiation treatment also increased viral replication and tumor cell killing [65,66].…”

Section: Hsv Combined With Conventional Therapiesmentioning

confidence: 91%

Advance in herpes simplex viruses for cancer therapy

Liu

Dai

You

et al. 2013

Sci. China Life Sci.

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Oncolytic virotherapy is an attractive approach that uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cell lyses through virus replication and cytotoxic protein expression. Herpes simplex virus (HSV) has become one of the most widely clinically used oncolytic agent. Various types of HSV have been studied in basic or clinical research. Combining oncolytic virotherapy with chemotherapy or radiotherapy generally produces synergic action with unclear molecular mechanisms. Arming HSV with therapeutic transgenes is a promising strategy and can be used to complement conventional therapies. As an efficient gene delivery system, HSV has been successfully used to deliver various immunomodulatory molecules. Arming HSV with therapeutic genes merits further investigation for potential clinical application.

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Radiation Therapy Potentiates Effective Oncolytic Viral Therapy in the Treatment of Lung Cancer

Cited by 49 publications

References 23 publications

Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1

Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells

Advance in herpes simplex viruses for cancer therapy

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