5 mei 2011: Bron: Pubmed

Via pubmed is een groot samenvattend studierapport in te zien dat een overzicht geeft van het gebruik van virussen en stamcellen (dendritische cellen) bij hersentumoren. Onderaan dit artikel staat de conclusie maar als u het hele studierapport wilt inzien klik dan hier. Bij het volledige studierapport staat een lange referentielisjt van vele studies gedaan met virussen bij met name hersentumoren.

23 januari 2006: Bron; Cancer Res. 2003 Jun 15;63(12):3162-72 en Oncolytics Biotech Inc.

Een injectie met reovirus verlengt leven van mensen met hersentumoren en remt en/of voorkomt uitzaaiïngen in de wervelkolom en verdere hersenuitzaaiïngen. Dit toont een tussenevaluatie aan van een Canadese fase I/II trial waarvan al eerder goede resultaten bekend werden gemaakt. Hier achtereenvolgens een artikel over deze studie en een abstract van verschillende dierstudies met reovirus die allemaal een significant positief resultaat laten zien.

Oncolytics Biotech Inc. Announces Conclusion of Patient Follow Up in Canadian Phase I Recurrent Malignant Glioma Clinical Trial

CALGARY, AB, --- January 17, 2006 - Oncolytics Biotech Inc. (“Oncolytics”) (TSX:ONC, NASDAQ:ONCY) announced today that the six-month follow up period has been concluded for patients in its Phase I Canadian recurrent malignant glioma clinical trial. As reported in October 2005, intratumoural administration of reovirus was well tolerated by the patients and a maximum tolerated dose was not reached. Surviving patients continue to be monitored and data analysis is ongoing.

“We intend to continue to investigate REOLYSIN® as a monotherapy in our U.S. Phase I/II malignant glioma clinical trial, employing an alternative delivery method,” said Dr. Brad Thompson, President and CEO of Oncolytics. “We are also considering the potential use of REOLYSIN® in combination with both the chemotherapeutics and radiation therapy that are the current standards of care for malignant glioma.” The study examined the use of a single, intratumoural injection of REOLYSIN®, delivered using imaging-guided surgery, in patients with malignant gliomas that had recurred despite other treatments, including surgery and radiation therapy. A total of 12 patients were treated in the study at dosages of 10(7), 10(8), and 10(9) TCID(50) in a delivery volume of 0.9 ml.

About Oncolytics Biotech Inc. Oncolytics is a Calgary-based biotechnology company focused on the development of REOLYSIN®, its proprietary formulation of the human reovirus, as a potential cancer therapeutic. Oncolytics’ researchers have demonstrated that the reovirus is able to selectively kill cancer cells and, in vitro, kill human cancer cells that are derived from many types of cancer including breast, bladder, prostate, pancreatic and brain tumours, and have also demonstrated successful cancer treatment results in a number of animal models. Previous Phase I clinical trial results have indicated that REOLYSIN® was well tolerated and that the reovirus demonstrated activity in tumours injected with REOLYSIN®.

This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including the Company’s expectations related to the results of the Canadian Phase I recurrent malignant glioma clinical trial and the US Phase 1/II trial investigating delivery of REOLYSIN® for recurrent malignant gliomas, and the Company’s belief as to the potential of REOLYSIN® as a cancer therapeutic, involve known and unknown risks and uncertainties, which could cause the Company’s actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of REOLYSIN® as a cancer treatment, the success and timely completion of clinical studies and trials, the Company’s ability to successfully commercialize REOLYSIN®, uncertainties related to the research and development of pharmaceuticals, uncertainties related to the regulatory process and general changes to the economic environment. Investors should consult the Company’s quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake to update these forward-looking statements.

Cancer Res. 2003 Jun 15;63(12):3162-72.

Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma.

Yang WQ, Senger D, Muzik H, Shi ZQ, Johnson D, Brasher PM, Rewcastle NB, Hamilton M, Rutka J, Wolff J, Wetmore C, Curran T, Lee PW, Forsyth PA.
Department of Oncology, University of Calgary and Tom Baker Cancer Centre, Calgary, Alberta, T2N 4N2 Canada.

Medulloblastoma (MB), the most common pediatric brain tumor, is a highly malignant disease with a 5-year survival rate of only 60%. Tumor cells invade surrounding tissue and disseminate through cerebral spinal fluid, making treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in tumor cells to support productive infection as an oncolytic virus. Here, we examined the ability of human reovirus to kill MB cells lines and surgical specimens in vitro and inhibit tumor growth/metastases in vivo. Most human MB cell lines tested (five of seven = 71.4%), two MB cell lines derived from spontaneously arising tumors in Patched-1(+/-) mice (two of two = 100%) and three MB primary cultures derived from surgical specimens, were susceptible to reovirus infection. Reovirus was internalized and transcribed in both susceptible and resistant cell lines. However, viral protein synthesis was restricted to cell lines with higher levels of activated Ras, suggesting that Ras plays a critical role in reovirus oncolysis in MB. Using an in vivo Daoy orthotopic animal model, we found that a single i.t. injection of reovirus dramatically prolonged survival compared with controls (160 versus 70 days, respectively; P = 0.0003). Repeating this experiment with GFP-labeled Daoy cells and multiple i.t. administrations of reovirus, we again found prolonged survival and a dramatic reduction in spinal and leptomeningeal metastases (66.7% in control injections versus 0.0% in the live virus group). These data suggest that this oncolytic virus may be a potentially effective novel therapy against human MB. Its ability to reduce metastases to the spinal cord could allow a reduction in the dose/field of total neuroaxis cerebral-spinal radiotherapy currently used to treat/prevent cerebral spinal fluid dissemination.

PMID: 12810644 [PubMed - indexed for MEDLINE]


Oncolytics Biotech Inc.
Brad Thompson
210, 1167 Kensington Cr NW
Calgary, Alberta T2N 1X7
Tel: 403.670.7377
Fax: 403.283.0858

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Virotherapy against malignant glioma stem cells

Bron: klik hier voor origineel volledig studierapport

Cancer Lett. Author manuscript; available in PMC 2011 March 1.
Published in final edited form as:
Published online 2009 July 29. doi: 10.1016/j.canlet.2009.04.045.
Transcriptional control of viral gene expression using tissue specific promoter has shown promising results in targeting just malignant cells and sparing normal tissue. This approach can be fine tuned by identification of stem cell specific promoters and thus designing vectors that drive transgene expression using these stem cell specific promoters. Cancer stem cells show marked similarity with normal stem cells, which represent the biggest challenge in the way of developing vectors driven by stem cell specific promoters. The same promoter that will drive viral gene expression in CSC, if present in normal stem cell, will also drive same viral gene expression in normal stem cells leading to normal stem cell lysis. Thus, it is critical to identify promoters that are not only specific for stem cell but restricted to CSC.
One of the hallmark features of glioma stem cells is the expression of a cellular surface glycoprotein containing five transmembrane regions and two glycosylated extracellular loops called CD133. Designing a viral vector that will specifically bind to CD133 will provide increased specificity in targeting these cells for virolytic therapy. However, one of the main limitations of this technique is the fact that CD133 is expressed not only in glioma stem cells but in other parts of the body. A recent study showed that human AC133 gene has at least 9 distinctive 5′-untranslated region (UTR) exons, resulting in the formation of at least 7 alternatively spliced 5′-UTR isoforms of AC133 mRNA, which are expressed in a tissue-dependent manner. Transcription of these AC133 isoforms is controlled by five alternative promoters, P1-P5 depending on their location relative to different exons, In vitro methylation of P1 and P2 completely suppresses their activity, suggesting that methylation plays a role in their regulation [94]. Finding the brain specific isoform of AC133 and directing vectors to the specific isoform will also increase the specificity of these vectors.
Optimal strategy for targeting glioma stem cells with viral vector will involve transduction of viral vectors in only CD133+ cells and transcription of viral gene driven by glioma specific promoter. Finally, the synergistic effect between virotherapy and chemo- and radiation therapy needs to be further evaluated to achieve optimal outcome for patients.

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