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Saturday July 04 2009 | Biotechnology feed | All feeds
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Return to introduction on drug discovery ~ LeadDiscovery Reports Oncolytic viruses offer hope in the treatment of metastatic brain cancer Oncolytic viruses have emerged from a period of intense research to offer real hope to cancer patients. As replication-competent and incompetent viruses start to demonstrate efficacy in the clinic researchers continue to optimize this approach. US-based researchers have recently made the breakthrough of applying blood brain barrier permeabilization technology to oncolytic viruses. Consequently they have for the first time been able to demonstrate the anticancer activity of systemically administered viruses in animal with metastatic brain cancer. Brain metastasis is increasing in incidence with improvements in systemic therapy increasing patient survival (see Brain Metastases - Markets, Treatments and Therapeutic Candidates). Up to 50% of cancer patients eventually develop brain metastases however current therapy is palliative and fails to impact on either declining quality or duration of life. Thus the brain metastasis market is characterized by a high level of unmet need, large patient potential and consequently high commercial value. Oncolytic viruses represent one treatment with the potential to meet this clinical need. Breast cancer is one of the most prevalent tumor types, largely
affecting women, but also a
Innovative targeted therapies currently dominate the pipeline, accounting for 70% of drugs in development for breast cancer and by the time these patent expiries have occurred several novel agents will have been commercialized. GlaxoSmithKline's dual kinase inhibitor, lapatinib, is currently the leading innovative breast cancer therapeutic. Analysts forecast blockbuster sales of $1.1 billion by 2012. A significant unmet component of breast cancer as well as many other cancers is brain metastasis, the incidence of which is escalating concurrent with improvements in systemic therapy increasing patient survival (see Brain Metastases - Markets, Treatments and Therapeutic Candidates). Up to 50% of cancer patients eventually develop brain metastases. Melanoma metastasises to the brain in up to 80% of patients at autopsy. The more common lung and breast cancers progress to the brain less frequently (10–20% of patients) however considering the overall incidence of these cancers, brain metastasis is very common. There is no approved pharmacotherapy for these patients and current therapy is palliative and fails to impact on either declining quality or duration of life. Median survival is four months. Thus the brain metastasis market is characterized by a high level of unmet need, large patient potential and consequently high commercial value. One therapeutic field offering promise for the treatment of metastatic brain cancer includes the oncolytic viruses. Oncolytic viruses are engineered to selectively replicate in cancer cells, or alternatively replication-incompetant viruses are engineered to selectively transfect cancer cells with anticancer vectors. Their selective nature is a key reason why oncolytic viruses are of potential benefit for metastatic disease. A number of different viruses have been developed for the
treatment of cancer, however herpes viruses (HSV) have been a focus of
particular attention. In our recent report
Developments in oncolytic viruses we evaluate a number of viruses
including MediGene's G207 and NV1020 as well as BioVex’s OncoVex and Crusade
Laboratories’s HSV1716, all developmental HSVs. The featured Gene Ther
report highlights a further oncolytic HSV, G47Delta which is derived from G207.
G207 was the first oncolytic HSV vector tested in humans in the
G207 has been further engineered to produce G47D, a mutant which characterized by enhanced viral growth (due to a mutation in the gene responsible for the shutoff of protein synthesis. Impeding viral mechanisms responsible for down-regulating MHC class I presentation by infected cells confers improved immunogenicity of infected cells. Consequently G47D is more efficacious than G207 in a number of subcutaneous tumor models, in immune-deficient and -competent mice, yet was similarly nontoxic after intracerebral injection. Although intracerebral administration of oncolytic viruses is viable in the clinic, systemically active viruses would have multiple and significant advantages. The blood brain barrier places a major limitation to systemic administration. Disruption of this barrier has been achieved in the clinic by intracarotid infusion of hypertonic solutions such as mannitol. This Gene Ther study reports that G47Delta was able to increase the survival of mice bearing intracerebral human breast tumors after the blood-brain barrier was disrupted through the use of mannitol to facilitate brain penetration. This procedure resulted in extensive viral replication in the tumor milieu while replication in peripheral organs, lung and liver, was minimal. Replication was mirrored by improved survival from 13 to 17 days. This is the first demonstration of intracarotid arterial delivery of oncolytic HSV vectors and antitumor efficacy in a mouse model. Medigene reported the initiation of a phase I/II trial of an oncolytic HSV virus, NV1020, in patients with colorectal cancer and liver metastasis in September 2004. Data from this study is eagerly awaited. Further improvements to oncolytic viruses should extend efficacy. The ability to target brain metastases represents one opportunity; likewise Biovex are developing an HSV based virus that are not only replication-selective but which are able to transfect cells with anticancer payloads (GM-CSF in the case of BioVex’s OncoVex virus). The field of oncolytic viruses is therefore one which continues to offer significant hope to cancer patients.
Entry date
Gene Ther. 2005 Jan 13; [Epub ahead of print] LeadDiscovery and BioPortfolio aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of LeadDiscovery and BioPortfolio may hold positions in some or all of the stocks discussed in this report. This abstract has been produced by LeadDiscovery Ltd. Founded by life scientists for life scientists we aim to help industry identify cutting edge drug discovery options and academic/biotech institutions maximize the potential of their research. Abstracts strictly reflect the opinion of LeadDiscovery's editorial panel. While all reasonable efforts are made to ensure the accuracy of information provided LeadDiscovery and the publisher BioPortfolio, takes no responsibility for incorrect or misleading information. LeadDiscovery is designed for educational and drug development purposes only and is not intended or designed to offer medical advice or advice of any sort, and must not be used for such purpose. The information provided through LeadDiscovery and BioPortfolio should not be used for diagnosing or treating a health problem or a disease and no reliance should be placed on any information contained in this abstract or elsewhere on LeadDiscovery's and BioPortfolio's website. It is not intended to be a substitute for professional care. If you have or suspect you may have a health problem, you should consult your physician or other health care provider. |
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