078 | Investing, combating and treating

Biotechnology Focus Podcast

Welcome to another episode of Biotechnology Focus radio. This week we are discussing a recent investment, the engineering of a CAR molecule to combat cancer, a new surgical treatment and a study notifying us that viruses are literally falling to Earth. I am your host Michelle Currie, here to bring you the lowdown on the Canadian biotech scene.

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Ontario Genomics is investing $100,000 in one of Toronto’s newest start-up companies, Bright Angel Therapeutics to develop anti-fungal treatments.

Fungal diseases are a growing global public health problem. Data compiled by the Global Action Fund for Fungal Infections shows that “over 300 million people are afflicted with a serious fungal infection and 25 million are at high risk of dying or losing their sight.” Mortality due to fungal infections is primarily due to the development of resistance to the few available anti-fungal compounds.

Ontario Genomics’ Pre-commercial Business Development Fund investment will help Bright Angel Therapeutics develop new compounds that are strategic to treating fungal infections. By targeting a stress response mechanism that enables fungi to become drug-resistant, this strategy will transform existing antifungals from ineffective to highly effective against all the leading fungal pathogens. Importantly, the stress response-targeting strategy being developed by Bright Angel enhances the efficacy of all three classes of current antifungal drugs. It is applicable to the leading causes of invasive fungal infection and prevents the emergence of drug-resistance. This strategy will allow the company to tap into the existing very large antifungal market.

Bright Angel Therapeutics was erected by Drs. Leah Cowan and Luke Whitesell, now both at the University of Toronto, based on technology developed while they were at the Whitehead Institute in collaboration with the late Dr. Susan Lindquist. With the assistance of MaRS Innovation, the company has partnered with Schrödinger Inc. to take advantage of Schrödinger’s world class molecular modeling and drug design expertise and will continue to provide start-up guidance.

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The Princess Margaret Cancer Centre in Toronto is leading a research team spearheaded by senior scientist Dr. Naoto Hirano that may have engineered a molecule that has the potential to augment existing immunotherapies.

This research is of relevance to chimeric antigen receptor (CAR) T-cell therapy – a therapy that uses a patient’s own immune cells (T-cells) identify and fight cancer cells. This study was published in the journal Nature Medicine.

In layman’s terms, CAR T-cell therapies help the immune system to recognize and destroy cancer cells through a process that begins with the isolation of T-cells from patients. Next, these cells are genetically modified so that they produce the CAR molecule on their surface. The CAR molecule is a modified version of a T-cell receptor that is specifically engineered to recognize tumour cells. These genetically modified cells are then grown in a lab to increase their numbers before being infused back into patients.

So far, CAR T-cell therapy has only been approved in the United States for blood cancers such as advanced lymphoma and acute lymphoblastic leukemia. This is believed to be because existing CAR

constructs don’t produce certain signals known to support the continued destruction of malignant cells, despite alerting the immune system of the presence of cancer.

Dr. Hirano’s team has engineered a molecule that activates specific protein signalling pathways which are known to enhance the growth and function of T-cells.

Hirano comments, “In our experimental models, the CAR molecule we engineered enabled T-cells to display more potent activity against different cancers, including solid tumours, which remain a challenge in the field. Current CAR T-cell therapies have shown limited success when treating solid tumours likely because of the harsh conditions faced by immune cells attempting to infiltrate the interior of the tumour. Furthermore, in these same models, we did not observe any worsening of potential side effects.”

While these findings are preliminary, the performance of the engineered CAR T-cells created by Hirano’s team suggests that optimizing CAR molecules may help to broaden the effectiveness of CAR T-cell therapies against different cancers. Work in the future will entail translating these findings into clinical trials to explore the safety and efficacy of the engineered CAR molecule.

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The Centre hospitalier de l’Université de Montréal (CHUM) is now offering a new surgical treatment for patients with lymphedema – swelling that is caused by the abnormal accumulation of lymph fluid in a body part, often the arms or legs.

Lymphovenous bypass surgery consists of microsurgically connecting the affected lymphatic vessels to the venous system to facilitate lymph fluid flow, decrease the severity of the lymphedema, reduce the complications related to this chronic disease and improve the quality of life of lymphedema patients.

The first lymphovenous bypass surgery to be performed at the CHUM took place on January 22, 2018, by Dr. Ali Izadpanah, on a 23-year-old man who developed secondary lymphedema following a motorcycle accident. For nearly three and a half years, Olivier Lagacé was limited in his movements because of the swelling in his left leg, which had nearly 35 per cent more volume than his right leg, despite continuous treatments (decongestive therapy and the wearing of compression socks). With the surgery performed at the CHUM, he will be able to hope for a reduction in not only the swelling in his leg, but in the number of treatments needed to control his illness. Lymphedema is a chronic disease for which there is currently no cure.

Lymphovenous bypass surgery was developed in Japan a few years ago and, although it is now available at many centres in the U.S., it is still not easily accessible by Canadians with lymphedema.

As a university hospital centre, the CHUM is presently working on developing a multidisciplinary clinical and research unit for lymphedema treatment that will make it possible not only to treat patients with this disease, but also to create a prospective database related to patients’ post-operative quality of life improvement. With its microsurgical simulation laboratory, which opened a year ago on the premises of the Direction de l’enseignement et de l’Académie CHUM, the hospital centre is also equipped and has set plans to contribute to lymphovenous surgery training and the development of new methods specific to this type of surgery.

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Although there are many things people would like to fall for – whether it be in love or for a joke – viruses are most likely not one of them.

Researchers from Canada, Spain and the US have discovered that there are a phenomenal number of viruses circulating around the Earth’s atmosphere – and they’re falling back to the ground every day.

This study marks the first-time scientists have quantified the viruses being swept up from the Earth’s surface into the free troposphere (layer of atmosphere beyond Earth’s weather systems but below the stratosphere where jet airplanes fly). The viruses can be carried thousands of kilometres there before descending back to the Earth’s surface.

University of British Columbia virologist Curtis Suttle, one of the senior authors of a paper in the International Society for Microbial Ecology Journal that outlines the findings says, “Every day, more than 800 million viruses are deposited per square metre above the planetary boundary layer—that’s 25 viruses for each person in Canada.”

This study brings to light how nearly identical viruses can traverse time and space and seemingly “pop up” around the globe.

Suttle adds, “Roughly 20 years ago we began finding genetically similar viruses occurring in very different environments around the globe. This preponderance of long-residence viruses travelling the atmosphere likely explains why—it’s quite conceivable to have a virus swept up into the atmosphere on one continent and deposited on another.”

Bacteria and viruses are swept up into the atmosphere mostly from natural methods like small particles in soil or dust and sea spray.

Suttle and colleagues at the University of British Columbia, the University of Granada and San Diego State University wanted to know how much of that material is carried up above the atmospheric boundary layer above 2,500 to 3,000 metres. At that altitude, particles are subject to long-range transport unlike particles lower in the atmosphere.

The researchers found that billions of viruses and millions of bacteria particles are falling to earth per square metre per day. They used the high altitude of Spain’s Sierra Nevada Mountains to calculate these findings with deposition rates for viruses being nine to 461 times greater than the rates of bacteria.

Bacteria and viruses are typically deposited back to Earth via rain events and Saharan dust intrusions. However, the rain was less efficient removing viruses from the atmosphere.

Hitching rides with smaller, lighter particles like sea spray, viruses have the ability to stay at loftier heights for longer and give themselves a farther reach. The findings are an eye-opener as to how pandemics and other viruses spread around the world. Now the problem remains – what will fall and when?

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Well that wraps up another episode of Biotechnology Focus radio. If you have any questions, comments or story ideas, please contact us at [e-mail], and don’t forget to follow us on our twitter handle @BiotechFocus.

I also wanted to mention that The 2018 Clinical Trials Conference hosted by Clinical Trials Ontario are taking place March 27-28, 2018 at the Sheraton Hotel in Toronto. It is an interactive and collaborative 2-day event that brings together over 350 people from industry, research, ethics, healthcare, non-profit, government and academia to exchange ideas, build relationships, and develop new strategies with respect to improving clinical trials and bringing more clinical trials to Ontario. For information about speakers, session topics, and registration, visit www.ctoconference.ca.

Hope you all have a great week! From my desk to yours – this is Michelle Currie.