Efficacy of a replication-selective adenovirus against ovarian carcinomatosis is dependent on tumor burden, viral replication and p53 status

Heise, Carla; Ganly, Ian; Kim, Y T; Sampson‐Johannes, Adam; Brown, Robert E.; Kirn, David H.

doi:10.1038/sj.gt.3301319

Cited by 64 publications

(32 citation statements)

References 22 publications

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“…In preliminary studies, this mortality appears to be due to liver toxicity, however the mechanisms (ie role of the HSVtk transgene, the possibility of viral replication within the liver, or possible toxicity due to intraperitoneal cytokine release) of this injury are unknown and are currently under study. It should be noted that similar early toxicity was not seen in the Wildner and Morris study 22 using E1B-deleted or wild-type viruses expressing HSVtk or by Heise et al 28 examining the use of the Onyx-15 virus in intraperitoneal models of ovarian cancer in nude mice.…”

Section: Discussionmentioning

confidence: 53%

Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy

et al. 2001

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Replication-incompetent adenoviruses (Ad) carrying the herpes simplex thymidine kinase (HSVtk) gene have been used in a number of human cancer gene therapy trials, however transduction has generally been limited to a small minority of tumor cells. To solve this problem, replication-competent adenoviral vectors carrying transgenes such as HSVtk have been developed. However, contradictory evidence exists regarding the efficacy of these new vectors. Accordingly, we constructed and tested a replication-competent E3-deleted adenoviral vector containing the HSVtk suicide gene driven by the endogenous E3 promoter (Ad.wt.tk). This virus

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Section: Discussionmentioning

confidence: 53%

Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy

et al. 2001

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“…4,5 The range of viruses showing promise as oncolytic therapies for ovarian cancer is quite broad and includes reovirus, Newcastle Disease virus, echovirus Type I, Sindbis virus, mumps virus and engineered adenoviruses. [6][7][8][9][10][11][12][13] We previously reported that a genetically modified measles virus expressing a soluble marker peptide (MV-CEA) is a potent and selective oncolytic agent, with promising activity in preclinical models of ovarian cancer. 14 MV-CEA targets and causes extensive fusion in ovarian cancer cells through the CD46 receptor, which is expressed at high levels by many tumor types, including ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model

Hadac

et al. 2006

Cancer Gene Ther

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Because of their ability to replicate, the dose-response relationships of oncolytic viruses cannot easily be predicted. To better understand the pharmacokinetics of virotherapy in relation to viral dose and schedule, we administered MV-CEA intraperitoneally in an orthotopic mouse model of ovarian cancer. MV-CEA is an attenuated oncolytic measles virus engineered to express soluble human carcinoembryonic antigen (CEA), and the virus is currently undergoing phase I clinical testing in patients with ovarian cancer. Plasma CEA levels correlate with numbers of virus-infected tumor cells at a given time, and were used as a surrogate to monitor the profiles of viral gene expression over time. The antineoplastic activity of single-or multiple-dose MV-CEA was apparent over a wide range of virus doses (10 3 -10 8 TCID 50 ), with little reduction in observed antitumor efficacy, even at the lowest tested dose. However, analysis of CEA profiles of treated mice was highly informative, illustrating the variability in virus kinetics at different dose levels. The highest doses of virus were associated with higher initial levels of tumor cell killing, but the final outcome of MV-CEA therapy at all dose levels was a partial equilibrium between virus and tumor, resulting in significant slowing of tumor growth and enhanced survival of the mice.

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“…These results showed that the intratumoral injection of ONYX-015 into primary pancreatic cancer was feasible and well tolerated at doses up to 10 11 PFU (2 Â 10 12 particles). However, viral replication was not detectable in biopsy specimens, 56 although other clinical trials using ONYX-015 detected viral replication in head and neck cancer, 57,58 ovarian cancer, 59 and in primary and secondary liver metastasis. 60,61 A phase I/II study using ONYX-015 for the treatment of pancreatic cancer was carried out in the Jonsson Comprehensive Cancer Center in Los Angeles, USA.…”

Section: Onyx-015mentioning

confidence: 82%

The potential of oncolytic virus therapy for pancreatic cancer

et al. 2005

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The objective of this paper was to review a new category of gene therapy using oncolytic viruses for the treatment of pancreatic cancer. The eligibility and feasibility of oncolytic virus therapy as a novel therapeutic agent against pancreatic cancer are discussed as well as basic research for clinical trials, including a historical perspective and the current status of these novel agents. Even combination therapy, such as surgery with radiation and chemotherapy, has not significantly improved the survival rate of pancreatic cancer. Recently, a clinical trial (phase I and II) using an oncolytic adenovirus, ONYX-015, was completed in patients with pancreatic cancer. The phase II trial yielded beneficial results (tumor reduction or stabilization) in about 50% of the patients. A phase I study of the efficacy of oncolytic herpes viruses, G207, OncoVEX GM-CSF, and 1716 against a variety of tumors has been completed, and G207 is in phase II trials for use against brain tumors. In addition, a phase I trial using the herpesvirus showed good tolerance at all dosages. We discuss the basic scientific principles and current results of the above clinical trials with respect to these oncolytic viruses, and then compare the relative advantages and disadvantages of adenoviruses and herpesviruses as oncolytic agents. We also review the published literature on newly developed oncolytic viruses. The concept of oncolytic therapy has been studied for a century. Recent technological developments have made these oncolytic viruses more tumor-specific by exploiting the tumor cell environments. In addition, these viruses have been reported to increase the immunosusceptibility of the tumor cells, and have been designed to express other genes to increase the susceptibility of tumor cells to other therapeutic agents. Oncolytic virus therapy certainly appears to be a feasible treatment for pancreatic cancer.

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Efficacy of a replication-selective adenovirus against ovarian carcinomatosis is dependent on tumor burden, viral replication and p53 status

Cited by 64 publications

References 22 publications

Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy

Inclusion of the herpes simplex thymidine kinase gene in a replicating adenovirus does not augment antitumor efficacy

Pharmacokinetics of oncolytic measles virotherapy: eventual equilibrium between virus and tumor in an ovarian cancer xenograft model

The potential of oncolytic virus therapy for pancreatic cancer

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