Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial

Park, Byeong Ho; Hwang, Tae-Ho; Liu, Ta‐Chiang; Sze, Daniel Y.; Kim, Jae‐Seok; Kwon, Hyuk Chan; Oh, Sung Yong; Han, Sang Young; Yoon, Jihyun; Hong, Sook Hee; Moon, Anne; Speth, Kelly; Park, Chohee; Ahn, Young Joo; Daneshmand, Manijeh; Rhee, Byung Geon; Pinedo, H.M.; Bell, John C.; Kirn, David H.

doi:10.1016/s1470-2045(08)70107-4

Cited by 461 publications

(447 citation statements)

References 28 publications

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“…One of which, the use of oncolytic viruses, has made significant progress in both pre-clinical and clinical development over the last 5 years. 2,3 As these therapies move into later stage clinical testing, and eventual approval, it is almost certain they will be combined with other therapies to maximize their effectiveness. A detailed understanding of which oncolytic viruses combine most effectively with traditional therapies, and the mechanisms underlying these effects are therefore needed.…”

Section: Discussionmentioning

confidence: 99%

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Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1

Huang

Sikorski

Kirn³

et al. 2010

Gene Ther

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Recent developments in the field of oncolytic or tumor-selective viruses have meant that the clinical applications of these agents are now being considered in more detail. Like most cancer therapies it is likely that they will be used primarily in combination with other therapeutics. Although several reports have shown that oncolytic viruses can synergize with chemotherapies within an infected cancer cell, it would be particularly important to determine whether factors released from infected cells could enhance the action of chemotherapies at a distance. Here, we demonstrate in vitro synergy between oncolytic vaccinia and taxanes. However, we also show, for the first time, that this synergy is at least partly due to the release of factors from the infected cells that are capable of sensitizing surrounding cells to chemotherapy. Several cellular factors were identified as being mediators of this bystander effect, including type I interferon released soon after infection and high-mobility group protein B1 (HMGB1) released after cell death. This represents the first description of these mechanisms for beneficial interactions between viral and traditional tumor therapies. These data may provide a direct basis for the design of clinical trials with agents currently in the clinic, as well as providing insight into the development of next generation viral vectors.

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Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6] One advantage of this approach is that viruses typically use distinct mechanisms of tumor cell killing relative to more traditional chemotherapy and radiotherapy approaches. 2 In addition, a variety of targeting mechanisms mean that different tumor phenotypic properties can be targeted with different viral strains.…”

Section: Introductionmentioning

confidence: 99%

Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1

Huang

Sikorski

Kirn³

et al. 2010

Gene Ther

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show abstract

“…in combination with low-dose cyclophosphamide (NCT01598129). 182 Intravenous or intratumoral JX-594 (a GM-CSF-expressing oncolytic poxvirus engineered to replicate in cells with specific oncogenic defects, also known as pexastimogene devacirepvec, Pexavec) 183 has been tested as single therapeutic agent in 15 subjects with colorectal carcinoma (CRC) (NCT01469611) 184 as well as in 14 pediatric patients with chemorefractory solid malignancies (NCT01169584). 185 The safety and efficacy of GL-ONC1 (a genetically modified vaccinia virus also known as GLV1h68) 186 have been evaluated in 14 individuals with malignant pleural effusion, who received intrapleural GL-ONC1 as standalone immunotherapeutic intervention (NCT01766739), 187 as well as in 19 subjects affected by HNC, who were treated with GL-ONC1 i.v.…”

Section: Completed Clinical Studiesmentioning

confidence: 99%

Trial Watch—Oncolytic viruses and cancer therapy

et al. 2015

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Oncolytic virotherapy relies on the administration of non-pathogenic viral strains that selectively infect and kill malignant cells while favoring the elicitation of a therapeutically relevant tumor-targeting immune response. During the past few years, great efforts have been dedicated to the development of oncolytic viruses with improved specificity and potency. Such an intense wave of investigation has culminated this year in the regulatory approval by the US Food and Drug Administration (FDA) of a genetically engineered oncolytic viral strain for use in melanoma patients. Here, we summarize recent preclinical and clinical advances in oncolytic virotherapy.

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“…This may allow VV to replicate in many different cell types and overcome the serious problem of more limited tropism encountered with adenovirus, another, more commonly used oncolytic vector (3,6). Oncolytic VV has demonstrated benefit in recent phase I/II clinical trials (7,8). These trials have indicated the inherent safety of the virus, efficacy of intravenous delivery of VV, VV infection of metastatic deposits, and reproducible disease control in many patients enrolled in the trials.…”

mentioning

confidence: 99%

Vascular Endothelial Growth Factor A Promotes Vaccinia Virus Entry into Host Cells via Activation of the Akt Pathway

Hiley

Chard

Gangeswaran

et al. 2013

J Virol

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Vaccinia virus (VV) is an enveloped DNA virus from the poxvirus family and has played a crucial role in the eradication of smallpox. It continues to be used in immunotherapy for the prevention of infectious diseases and treatment of cancer. However, the mechanisms of poxvirus entry, the host factors that affect viral virulence, and the reasons for its natural tropism for tumor cells are incompletely understood. By studying the effect of hypoxia on VV infection, we found that vascular endothelial growth factor A (VEGF-A) augments oncolytic VV cytotoxicity. VEGF derived from tumor cells acts to increase VV internalization, resulting in increased replication and cytotoxicity in an AKT-dependent manner in both tumor cells and normal respiratory epithelial cells. Overexpression of VEGF also enhances VV infection within tumor tissue in vivo after systemic delivery. These results highlight the importance of VEGF expression in VV infection and have potential implications for the design of new strategies to prevent poxvirus infection and the development of future generations of oncolytic VV in combination with conventional or biological therapies.

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Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial

Cited by 461 publications

References 28 publications

Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1

Synergistic anti-tumor effects between oncolytic vaccinia virus and paclitaxel are mediated by the IFN response and HMGB1

Trial Watch—Oncolytic viruses and cancer therapy

Vascular Endothelial Growth Factor A Promotes Vaccinia Virus Entry into Host Cells via Activation of the Akt Pathway

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