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We blog about science from our own lab, and labs around the world!

By stojdllab, Dec 21 2015 07:14PM

In a cool new study released from the Mayo clinic, oncolytic vesicular stomatitis virus (VSV) was infused into mice with myeloma that had either just exercised (high blood pressure; 'EX') or were anaesthetised (low blood pressure; 'ISO').

Mice that had a higher blood pressure during intravenous perfusion showed a greater density of virus reaching the tumour site. Virus was also spread across the tumour in a more uniform pattern.

The mice receiving virus treatment at a higher blood pressure also had a significantly longer survival time (see graphs above; top=survival curves, bottom=individual tumour sizes).

These results have potential positive implications for patients undergoing oncolytic viroimmunotherapy, since raising the blood pressure is easily achieved prior to virus infusion without the need for additional drugs or interventions.

Image: Miller et al 2015

By stojdllab, Nov 16 2015 10:33PM

Tumours typically recruit regulatory T cells (Tregs) to suppress the activity of other T cells. This effectively prevents T cells from targeting - and destroying - the tumour. Now, a team of scientists from Harvard Medical School have shown that overexpressing a fragment of a protein called Notch 1 in Tregs reverses their activity - and helps them promote T cell function. Although this team's research is based in a model of immune tolerance, it has key (positive) implications for cancer immunotherapy strategies.

You can read the original research paper in full here.

Image credit: Scientific Illustration for the Research Scientist

By stojdllab, Oct 21 2015 04:27PM

Regulatory T cells, or Tregs, are immune cells that are typically considered bad news for cancer patients. That’s because these cells are immunosuppressive, and can prevent the patient’s other immune cells from attacking and clearing their tumour. Essentially, the Tregs are recruited by the tumour to act as a protective shield.

Yet new research from scientists in China suggests that Tregs aren’t always bad. In some cancers, the presence of many Tregs in the tumour can actually correlate with improved survival.

Taken directly from their new paper, the risk graph above shows that patients with cervical, renal, skin, liver, gastric and breast tumours that were densley packed with FoxP3+ Tregs had a significantly shorter overall survival (their ‘risk’, which is numerically considered along the horizontal axis, is greater). Yet increased infiltration of FoxP3+ Tregs was associated with improved overall survival for colorectal, head and neck, and oesophageal cancer patients.

Read the original (open access) article in full here.

By stojdllab, Sep 8 2015 03:39PM

Tumours often overproduce prostaglandin E2 (PGE2) to help them to grow faster. A common drug in most people’s medicine cabinets, aspirin, is actually a COX inhibitor that can block the production of PGE2 and help reactivate a patient’s own immune system against their tumour.

Read the original article here.

Image: Zelenay et al 2015

By stojdllab, Jul 10 2015 02:00PM

The Stojdl Lab's clinical trial, in one glorious infographic
The Stojdl Lab's clinical trial, in one glorious infographic

An immune-stimulating cancer-killing virus therapy has made its debut treating cancer patients in Ottawa, Canada.

The therapy was jointly developed by Dr. David Stojdl (Children’s Hospital of Eastern Ontario, University of Ottawa), Dr. Brian Lichty (McMaster University) and Dr. John Bell (The Ottawa Hospital, University of Ottawa) and their respective research teams and colleagues. The clinical trial, which is funded by the Ontario Institute for Cancer Research and coordinated by the NCIC Clinical Trials Group, is expected to enroll up to 79 patients at four hospitals across Canada.

The trial is designed to test two viruses, MG1MA3 and AdMA3, administered as either single or double treatments. MG1MA3 is derived from Maraba virus, which was identified as an oncolytic agent in 2006 by Dr. Stojdl and his team at the Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa.

Dr. Stojdl described the process that led to this discovery: “We had gone looking for a "next generation" oncolytic virus by sifting through a panel of viruses identified all over the world. When the data started pouring in, Maraba jumped out as the most potent tumour killer we had ever seen.”

The second virus, AdMA3, is derived from a common cold virus called adenovirus, and has been developed as an immune-stimulating agent for combination cancer therapy by Dr. Lichty and Dr. Yonghong Wan at McMaster University, Hamilton.

Both of these viruses have been re-designed to bolt on extra hardware designed to stimulate the patient's own immune system against a protein called MAGE-A3. This protein acts as a beacon that lights up the patient's tumour to guide immune destruction. The Maraba virus also achieves an extra layer of anti-cancer activity by replicating inside many kinds of cancer cells and killing them directly.

A four-institute academic partnership has driven this technology to reach patients. The dual virus platform, designed between the CHEO RI, McMaster University and the Ottawa Hospital Research Institute (OHRI) was developed into a clinical-grade drug using a world-class virus manufacturing infrastructure helmed by Dr. John Bell at the OHRI, and McMaster University, with support from the Ontario Institute for Cancer Research (OICR).

Dr. Stojdl thinks the four partners have now created a great cancer-fighting weapon. As he highlights, "A really difficult issue in cancer is dealing with a disease that morphs over time and in response to treatment. Having a therapy that can attack from multiple angles all at once is key to addressing this challenge. Our Maraba virus vaccine technology has proven to be a purpose built multi-purpose tumour killer that adds anti-cancer power without adding toxicity". He adds: "we, and our supporters, are thrilled to see this therapy finally start to reach cancer patients".

The founding scientists and their institutions, in co-operation with the Fight Against Cancer Innovation Trust, have also formed the biotechnology company, Turnstone Biologics, in order to engage the private sector and advance the development of these therapies into new clinical trials. As Dr. Stojdl highlighted, "We’re continuing to push very hard to develop a suite of biological therapies with the goal of launching similar trials tailored to other types of tumours, including brain cancer and several devastating childhood cancers". Dr. Bell and his colleagues also recently launched the $60M BioCanRx National Centres of Excellence network to advance research into cancer biotherapies and immunotherapies.

The trial is recruiting patients at sites across Canada, including the Ottawa Hospital (Ottawa), the Juravinski Cancer Centre (Hamilton), the Princess Margaret Cancer Centre (Toronto) and the British Columbia Cancer Agency (Vancouver). It is primarily funded by the Government of Ontario through the Ontario Institute for Cancer Research; many other funding organizations have also supported the research of Drs. Bell, Lichty and Stojdl, including the Ottawa Hospital Foundation, CHEO Foundation, Canadian Cancer Society, Terry Fox Research Institute, Canadian Institutes of Health Research, Ontario Ministry of Research and Innovation, Canada Foundation for Innovation, Ottawa Regional Cancer Foundation, Hair Donation Ottawa, Angels of Hope, BioCanRx, Pancreatic Cancer Canada, and several philanthropic donors.

Image credits: somersault1824​, David Goodsell, Cronodon

The original press release is available on the Children's Hospital of Eastern Ontario Research Institute website. Further details about the trial are available at clinicaltrials.gov. Patients wishing to participate in the trial should speak with their own oncologist and ask for a referral to one of the participating hospitals. Further details for patients at The Ottawa Hospital are available online.

You can find out more about the Stojdl lab on Twitter, Facebook, Tumblr and YouTube, or online at www.stojdllab.ca.

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