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Global Health News and Reports

Revealed — Mosquito genes that could be controlling the spread of killer viruses

Contact: Danielle Reeves
danielle.reeves@imperial.ac.uk
44-020-759-42198
Imperial College London

The genes that make up the immune system of the Aedes aegypti mosquito which transmits deadly viral diseases to humans have been identified in new research out today in Science.

The immune system of this mosquito is of great importance as scientists believe it plays a key role in controlling the transmission of viruses that cause yellow and dengue fevers – diseases that infect over 50 million people worldwide every year.

This study is the first of its kind on the newly-sequenced genome of the Aedes aegypti mosquito, which is also published in this week’s Science. The researchers identified over 350 genes which are involved in the Aedes mosquito’s immune system, and discovered that they evolve much faster than the rest of the genes in the genome. Identifying which of these key genes are implicated in the transmission of viral diseases is an area of future research that could lead to new ways of combating these diseases. One possibility would be to affect the activity of the genes and therefore help the mosquitoes fight off the viruses more effectively, preventing transmission to humans.

Imperial College scientists participating in this study established previously that other mosquitoes do have a robust immune system that can either allow or block transmission of malaria parasites. Further research will be needed to ascertain whether some of the newly discovered genes in Aedes may provide a similar defence mechanism that can fight the disease viruses.

Dr George Christophides of Imperial’s Division of Cell and Molecular Biology, senior author on the paper explains: “Our study has revealed the genetic ‘landscape’ made by parts of this mosquito’s newly-sequenced genome which are involved with immunity. By working to understand as much as possible about these genes, and the way they interact with specific pathogens, we hope to gain a more complete understanding of the mechanisms by which a pathogen either survives inside the insect body, or is killed by the insect’s defences.”

The international research team, led by Imperial PhD student Robert Waterhouse, focused on comparing the immunity genes of the Aedes mosquito with similar groups of genes in the harmless fruit fly and the Anopheles mosquito that transmits malaria. When comparing the two different mosquitoes, the scientists found some similarities in the genes controlling their respective immune systems, but also numerous differences. The team aims to discover which of these genetic differences could explain why one type of mosquito transmits dengue and yellow fevers, while the other transmits malaria. Beyond the present descriptive work, functional studies will be needed to clarify exactly how this happens.

“This study made us realise that the immune systems of insects are not static but evolve and differentiate rapidly, most likely in response to the different pathogens which each insect species encounters”, says Dr Christophides.

Professor Fotis Kafatos, senior researcher of Imperial’s immunogenomics lab and co-author of the paper, explains the significance of their study, saying: “Understanding the genetics behind pathogen/immune system interactions in disease vector mosquitoes may help us understand why, for example, some types of mosquitoes can transmit a particular human pathogen while others cannot. If those that cannot have evolved an effective immune system that fights off the pathogen, we may be able to use this knowledge to enhance specific reactions of the immune systems in other mosquitoes to control the spread of the disease.”

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June 22, 2007 Posted by | Genes, Genetics, Global, Global Health Vision, Global News, Imperial College London, Molecular Biology, News, News Australia, News Canada, News Israel, News Jerusalem, News UK, News US, Research, Virginia, Viruses, Washington DC, World News | Leave a comment

Dealing deadly cancers a knockout punch

Contact: Cathy Ward
cathy.ward@oncolyticsbiotech.ca
403-670-7370
Oncolytics Biotech Inc.

New scientific evidence is helping to build a compelling case for oncolytic viruses as a first-line and adjunctive treatment for many cancers.

Reovirus, a non-pathogenic virus under development at Calgary, Alberta-based Oncolytics Biotech, has shown powerful anti-cancer activity against cultured tumor cells, in animal models, and in human clinical trials. Oncolytics’ proprietary reovirus formulation, Reolysin®, is active against numerous cancers, including intractable sarcomas and melanomas.

Recent studies also indicate that Reolysin works synergistically with standard anti-cancer drugs, providing significantly stronger responses than either agent alone.

In addition, other studies completed in the past year have shown Reolysin has the ability to prime patients’ immune systems against their particular cancer, leading to additional cancer cell killing. It is through this second “inflammatory” mechanism that researchers hope Reolysin will bring about long-term remissions of once-untreatable cancers.

At the Fourth International Conference on Oncolytic Viruses as Cancer Therapeutics in March 2007 in Scottsdale, Arizona, several presentations focused on reovirus efficacy alone or in combination with standard chemotherapies.

In one study, investigators examined the tumor-killing ability of reovirus plus cisplatin, a standard chemotherapy agent, in a mouse melanoma model that included both cultured cells and live animals. The results of the preclinical study showed that the combination of reovirus and cisplatin was significantly more effective than cisplatin or reovirus alone at killing melanoma cancer cells in a mouse model. The investigators intend to explore the mechanism of this promising synergistic action in further detail in future preclinical work.

Another presentation at the Arizona conference reported on the use of Reolysin plus the cancer drug cyclophosphamide in an animal model of melanoma. When treated with both agents, test animals experienced enhanced tumor regression compared with either agent alone, and without additional toxicity. Oncolytics has permission from the U.K. regulatory authorities to test Reolysin in three separate human trials in combination with the cancer drugs gemcitabine, paclitaxel/carboplatin and docetaxel.

Perhaps the most exciting findings of Reolysin combination therapy were reported at the American Association for Cancer Research Annual Meeting in April, 2007. In mice transplanted with a human colon cancer, Reolysin plus gemcitabine completely eradicated the tumors in four of five test animals. It is rare to see the virtual elimination of tumours as well as the long-lasting therapeutic effect that was observed in this study.

“Combination therapy results for reovirus in animals are particularly encouraging because they suggest that Reolysin can improve the anti-tumor activity of standard chemotherapy agents in advanced cancer patients without causing additional toxicity,” said Dr. Karl Mettinger, Chief Medical Officer of Oncolytics.

Physicians often prefer to treat cancer with multiple agents, but toxicity limits these approaches. Since reovirus typically is not pathogenic in humans nor associated with severe toxicity in clinical studies, its co-administration is not expected to increase a treatment’s overall toxicity.

Dual Mechanism

Reovirus works by entering and replicating within cancer cells containing an activated ras pathway, a mutation present in about two-thirds of all human cancers. Reovirus enters a cancer cell, makes thousands of copies of itself, and then causes the cell to burst, which releases viruses that infect and kill adjacent cancer cells. Normal cells are not harmed.

In addition to killing cancer cells directly, reovirus is believed to activate an anti-tumor immune response through the body’s natural killer cells and T cells. Through this mechanism, which persists for weeks or months, the body continues to fight off cancer long after the virus clears from the body.

Future directions

On April 11, 2007, Oncolytics announced it had initiated a Phase II trial to evaluate intravenous administration of Reolysin in patients with sarcomas that have metastasized to the lung. For patients with deadly soft tissue sarcoma, the lungs are the most common site of metastatic disease. To date, surgery has been the only effective therapy for metastatic sarcoma.

The multi-center, Phase II study follows successful completion of systemic administration trials with Reolysin in the U.K. and the U.S. This will be the second of several Phase II trials Oncolytics plans for 2007. The Company also has a collaborative agreement with the U.S. National Cancer Institute to conduct multiple clinical trials with Reolysin which are expected to begin in 2007, including a Phase II melanoma trial and a Phase I/II ovarian cancer trial.

“It is hoped that the trials will clearly show that Reolysin alone or in combination with either radiation or chemotherapy can stop or reverse the growth of advanced cancers without adding harmful side effects,” said Dr. Mettinger.

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May 10, 2007 Posted by | Alberta, Calgary, Cancer, Clinical Trials, Global, Global Health Vision, Global News, Oncology, Viruses | Leave a comment