CanPath partnership sheds light on COVID-19 immunity across Canada

Study untangles relationship between vaccination status and infection risk.

New findings from a Canada-wide collaboration that includes CanPath (the Canadian Partnership for Tomorrow’s Health) show that more than three quarters of people in Canada now have immunity to the virus that causes COVID-19 through prior infection.

The study, published in the Canadian Medical Association Journal (CMAJ) by the COVID-19 Immunity Task Force (CITF), is the first peer-reviewed publication showcasing pan-Canadian estimates of seroprevalence, which refers to how many people have developed antibodies in response to infection or vaccination.

“We aimed to untangle the relationship between vaccination status – including the number of doses, brands, and time between doses – and infection risk while accounting for prior infection, adherence to recommendations from public health officials and other factors which impact immunity such as age,” says Dr. Kimberly Skead, National Scientific Coordinator for CanPath.

CanPath, which is hosted by OICR, is the country’s largest population health study. In 2020, CanPath and partners across the country were tasked by CITF and the Public Health Agency of Canada (PHAC) to develop and support a national COVID-19 serological surveillance study.

CanPath has since collected COVID-19 data from over 100,000 Canadians at three different time points up until March 2023.

“CanPath’s extensive participant base has been instrumental in enabling us to find these differences in exposure and immunity across Canada,” says Dr. Philip Awadalla, National Scientific Director for CanPath, Professor of Molecular Genetics at the University of Toronto and Director of Computational Biology at OICR. “The results from our studies, combined with the wealth of data and ongoing research from our collaborators, can contribute to different vaccine responses as the pandemic progresses.”

Using aggregate data from various collaborating pan-Canadian teams, the CITF estimated infection- and vaccine-related seroprevalence trends. In the pre-vaccination and vaccine roll-out phases, few people showed SARS-CoV-2 infection in their blood – 0.3 per cent and nine per cent respectively.

But in mid-June 2022, infection rates increased to 47 per cent. Then they increased to 75 per cent by March 2023. Infection appears to be slowing, though it continues to rise amongst older adults.

Researchers say that certain measures can be taken to ensure that our ongoing narrative remains one of resilience, adaptability, and safeguarding our collective well-being.

“Given the lingering risks of post-COVID conditions and the vulnerability of certain individuals to severe outcomes, a proactive approach is essential,” says Dr. Victoria Kirsh, Scientific Associate at the Ontario Health Study, Assistant Professor at the Dalla Lana School of Public Health. “To safeguard against future variants, it’s important to continue monitoring COVID-19’s spread and roll out booster campaigns ahead of upcoming waves.”

This was adapted from an article by CanPath (the Canadian Partnership for Tomorrow’s Health).

The Next Generation: Tom Ouellette

PhD student harnessing computational tools to make a difference for cancer patients.

Tom Ouellette wouldn’t have predicted that he’d pursue cancer research.

However, he had an interest in computational tools and wondered how they could be harnessed to study biological questions, which led him to undertake a PhD in Computational Biology at the University of Toronto. It wasn’t until he rotated into Dr. Philip Awadalla’s lab at OICR that Ouellette became passionate about studying cancer.

Now, he’s using that passion to build computational tools to predict how cancer progresses – tools that hopefully one day make a difference for cancer patients.

“I was confronted with this sobering fact that almost everyone will know someone that has cancer,” Ouellette says. “This turned my pure biological interest in cancer research to something where I want to build tools that matter for a patient’s journey.”

Find out more in Ouellette’s The Next Generation video.

OICR introduces groundbreaking test proven to find traces of cancer in blood

The highly sensitive Plasma Whole Genome Sequencing assay is available for clinical research studies for any tumour type through OICR’s accredited genomics lab.

A new blood test proven to detect residual signs of cancer could revolutionize how treatments are monitored and assessed, and it’s now available to research studies through the Ontario Institute for Cancer Research (OICR).

OICR Genomics’ Plasma Whole Genome Sequencing assay tests patients’ blood for the unique molecular fingerprint of thousands of mutations unique to their individual cancer. This broad approach enables highly sensitive detection of tiny pieces of tumour DNA that are shed into the bloodstream by cancer cells — a sign that cancer is still present even when it’s not detectable with other tests.

Tests that use blood samples, known as ‘liquid biopsies’, are an exciting alternative to traditional biopsies because collecting blood samples is easier and less invasive than surgical removal of tumour tissue.

“We have been sequencing whole genomes from tumours for three years now,” says Dr. Trevor Pugh, OICR Senior Investigator and Director of Genomics. “This test is an evolution of that capability to start looking for fragments of the cancer genome in blood at an extremely low level. Now, we can support a whole new type of clinical trial design whereby a blood sample can tell a physician very early on whether an initial treatment is working or whether a patient should be expedited to an alternate therapy.”

The test, which is currently only available to clinical trials, works in conjunction with OICR’s other genome sequencing services. Patients can have DNA from a tumour sample sequenced to help diagnose their cancer and direct them to a personalized treatment. Then they can have a blood sample taken during or after their treatment to see how effective it was, and whether their cancer is likely to recur.

Because the test can detect even a small number of cancer cells, it can help find cancer recurrence early so that it can be treated before it comes back fully.

Developed by OICR Genomics over the past 14 months, the Plasma Whole Genome Sequencing assay meets all standards for accuracy, sensitivity, specificity, and reproducibility. It adds to OICR Genomics’ world-leading genomics services, which include the latest in whole genome and transcriptome sequencing technology.

“The most challenging part of validating these tests is having matched, high-quality blood and tumour samples for comparison. We were fortunate to collaborate closely with the OCTANE study at the Princess Margaret Cancer Centre that had the foresight to bank blood plasma samples perfectly matched to the tissues used to validate our original tumour test,” Dr. Pugh added.

OICR Genomics is also the first lab in North America to be accredited by the three major accreditation organizations for whole genome and transcriptome sequencing: Clinical Laboratory Improvement Amendments (CLIA), the College of American Pathologists (CAP) and Accreditation Canada Diagnostics (ACD).

“This means that researchers and clinicians can feel confident that our services meet the highest possible standards,” says Dr. Carolyn Ptak, Senior Program Manager and Quality Assurance Lead for Genomics at OICR. “And this new assay is no exception.”

“This world-first assay is an exciting development for clinical research in Ontario and around the world, and a major step forward in our ability to provide personalized treatment to everyone with cancer,” says OICR President and Scientific Director Dr. Laszlo Radvanyi. “It is another example of how OICR is leading the charge in developing innovative and cutting-edge technologies that benefit cancer patients. Congratulations to OICR’s Genomics team and everyone who made this tremendous achievement possible.”

Find out more on the OICR Genomics website.

Ask a Cancer Researcher: What happens to samples donated to tumour banks?

Dr. Dianne Chadwick, Associate Director of the Ontario Tumour Bank (OTB), answers an interesting question from the public.

Before she had cancer surgery, Diana Lemaire was asked if she wanted to donate her tumour to a tumour bank so that it could be used in cancer research.

So she was wondering: what happens to tumours that are donated to a tumour bank?

Ontario Tumour Bank Associate Director Dr. Dianne Chadwick provides the answer in the latest instalment of our Ask a Cancer Researcher video series.

See her answer below and submit your own question if you’d like to be featured in an upcoming video.

The ‘incredible’ way the HPV virus causes cancer and what that means for treating it

OICR-supported research could open new avenues to treat cancers of the cervix, head and neck.

The human papillomavirus (HPV) is the driving force behind most cancers of the cervix, head and neck thanks to its unique ability to hijack the human chromosome.

OICR-supported research has uncovered new details about how that hijacking happens and could provide a roadmap for how to stop it.

“HPV has the incredible ability to integrate itself into a human’s chromosomes,” says Dr. Michael Hoffman, a Senior Scientist at Princess Margaret Cancer Centre who led the study with colleagues Dr. Mathieu Lupien (an OICR Investigator) and Dr. Scott Bratman. “Our study focuses on how that integration, and where it takes place, can contribute to cancer.”

The study, published in Genome Biology, describes how HPV DNA inserts itself into its host’s genome and ‘rewires’ the activity of nearby genes.

“When the rewired genes normally play a role in stopping abnormal growth, this can result in cancer,” Hoffman says.

The virus works on human cells by ‘loosening’ chromatin, a ‘package’ of DNA which is normally tightly packed into a cell’s nucleus. This gives the virus access to a cell’s DNA and allows it to make changes to the proteins that regulate cell growth.

“We found that by hijacking the epigenetic machinery of the cell, HPV can induce everlasting changes in a chromosome that predispose to cancer,” says Dr. Mehran Karimzadeh, first author of the study, who performed the research while a PhD student at Princess Margaret Cancer Centre.

Hoffman says his group’s findings about HPV changing human DNA are unique from other studies into HPV and cancer, which have focused largely on the role of HPV’s own DNA. By describing this pathway through which HPV causes certain cancers, this new study could help discover new ways to treat those cancers.

“What we discovered in this study, when combined with DNA sequencing technology, could lead to better assessment of cancer prognosis and more informed treatment decisions,” Hoffman says.

Paying it forward with a patient perspective

Carla Bossart-Pletzer joined OICR’s Patient and Family Advisory Council to help others with cancer overcome the odds, just like she did.

In a matter of a few weeks, Carla Bossart-Pletzer went from visiting the emergency department about a high fever and stubborn rash on her breast to learning she had one of the most aggressive forms of breast cancer.

It was a whirlwind with a shocking result: inflammatory triple negative breast cancer, which has a much lower survival rate than other types of breast cancer.

But Bossart-Pletzer barely had a chance to be shocked. Within days, she was starting chemotherapy to try and shrink her tumour before surgery — a new treatment approach that had only recently become the standard of care.

In the meantime, her scans for metastatic cancer came back clean. By the time she had surgery six months later, doctors found her tumour had shrunk to a fraction of its former size and no evidence of cancer remained her in lymph nodes.

In many ways, everything went right with Bossart-Pletzer’s cancer treatment. Her healthcare providers acted quickly, and her treatment did exactly what it was supposed to.

“All the systems went exactly as they should,” says Bossart-Pletzer, a designer and illustrator based in Sudbury. “Here I am, 18 months later, with no evidence of cancer.”

But her experience with cancer was far from perfect. She still had to go through a year and a half of aggressive treatment that left her with lingering side effects, and she found that the way things operated in the hospitals and cancer centres she visited didn’t feel quite right.

She’s also very aware that things could have gone very differently under other circumstances.

“I have this feeling. Maybe it’s survivor’s guilt,” Bossart-Pletzer says. “But I look at what cancer research has done for me, and how it has changed my future. Now, what can I do to ensure that other people have the same results?”

Just a year and a half since her diagnosis, Bossart-Pletzer is taking action to answer that question by becoming a Patient Advisor and building patient involvement at Health Sciences North in Sudbury and, more recently, joining OICR’s Patient and Family Advisor Council (PFAC). OICR News recently asked her about her early days on PFAC and what she hopes to achieve.

You mentioned that the success of your cancer treatment motivated you to want to give back. Can you tell us more about that?

I think a lot about why things worked so well for me. I know part of it is because I lived in Sudbury, where we have an impressive cancer centre and I was well connected to healthcare people. I also know it’s partly because, as a white woman, I was taken seriously by healthcare providers and was treated expeditiously. Because the reality is, when you look at the statistics with inflammatory breast cancer, it disproportionately affects women of colour in their thirties and forties and is almost always diagnosed at the metastatic stage. So, there’s a certain obligation I feel to make sure that system works as well for others as it did for me.

Is there any area of cancer research that you’re particularly interested in?

I’m still in the early days with OICR, but I’m finding I’m really interested in improving access to clinical trials. As somebody from Northern Ontario, it sometimes seems that people forget that Ontario continues north of Barrie. There’s a huge population of people up here that don’t have access to clinical trials that could help save their lives.

What other impact would you like to have as a patient partner?

I think there’s a misconception that cancer only happens to people under 18 or over 65. But there are unique challenges that come with being a young adult with cancer, and I’d like to bring more attention to them.

For example, I’m only just now able to return to work after a year and a half of treatment. Add that to being a mother in my 30s coming out of a pandemic, and it means every dollar is important. Unfortunately, I had to pay out of pocket for some parts of my treatment. And I was sometimes faced with choices like: do I pay for chemo pills, or do I put my kids in soccer?

How has being a mother influenced the way you approach being a patient partner?

As part of my breast cancer diagnosis, I found out that I have the BRCA1, MSH-6 and ATM genetic mutations, which are hereditary. I have a four-year-old daughter. What is her life going to look like in the future? What decisions is she going to have to make when she turns 18 because she’s scared of getting cancer like her mom? Will I still be alive to help her make those decisions? I don’t know. So, I’m in this window of opportunity to do what I can to make things better for her and for others who may get this cancer in the future.

Fecal transplants bolster melanoma treatment in unique clinical trial

A trial led by OICR Investigator Dr. Saman Maleki used fecal microbiota transplants (FMT) to improve how melanoma patients respond to immunotherapy.

People with advanced melanoma who get a fecal transplant before starting immunotherapy could have better results from treatment, according to a promising clinical trial.

In the trial, published in Nature Medicine, patients were given what is called a fecal microbiota transplant (FMT) from a healthy donor in the hopes of improving their gut health before starting immunotherapy, a new type of treatment that stimulates the body’s immune system to kill cancer.

Currently, immunotherapy works for less than half of patients with advanced melanoma, and side effects can be severe. But earlier research showed a healthy gut microbiome triggers a stronger response to immunotherapy.

“We need treatments for melanoma that we can add to existing immunotherapies to improve overall patient response without adding too much toxicity,” says lead investigator Dr. Saman Maleki, a Scientist at Lawson Health Research Institute, Assistant Professor at Western University’s Schulich School of Medicine and an OICR Investigator. “Our study shows that FMT could be a safe and effective option.”

A total of 20 patients from across Ontario and Quebec were recruited for the trial at the Lawson Health Research Institute, the Centre hospitalier de l’Université de Montréal (CHUM) and the Jewish General Hospital (JGH). They were given FMT in capsule form one week before starting immunotherapy.

About 65 per cent of participants saw their cancer improve during the trial, which is higher than the response rate expected from immunotherapy alone (30-40 per cent). Four patients had their cancer disappear completely during the trial — a result Maleki calls ‘remarkable’.

“We are very encouraged by the strong response profile that we observed in this cohort of patients,” he says.

The results also showed that using FMT this way is safe and doesn’t add any additional side effects beyond what is expected from immunotherapy. In fact, FMT may help reduce some immunotherapy side effects, and that potential is being explored in another different clinical trial.

Maleki and colleagues are already working on a larger clinical trial to further explore the effect of FMT and immunotherapy on melanoma. Similar studies are also underway using fecal transplants to treat renal cell carcinoma, lung cancer and uveal melanoma, and there are plans for trials that target pancreatic cancer and breast cancer.

“When I came up with the idea of prospective microbiome modulation in cancer patients in 2016, there was not much enthusiasm in the oncology community,” Maleki says. “Now, we’ve opened the door to using FMT in other cancers in early settings, which could potentially change how cancer patients are treated with immunotherapy drugs in the future.”

This research is supported in part through donor funding from London Health Sciences Foundation, Western University, the Lotte and John Hecht Memorial Foundation, the JGH Foundation, Canadian Cancer Society’s Impact Grant program, The Terry Fox Foundation and OICR’s Investigator Awards. More information is available in an announcement from the Lawson Health Research Institute.

New framework aims to drive innovation by making health data management ‘FAIR’

OICR’s Dr. Mélanie Courtot was part of a global effort to make data more findable, accessible, interoperable and reusable (FAIR).

Health data holds the key to overcoming major public health challenges, but only if it is accessible when people need it.

The world learned this lesson the hard way during the COVID-19 pandemic, when problems like missing data, service incompatibility and data access restrictions delayed research that could have helped the global public health response.

But an international collaboration, led in part by OICR’s Dr. Mélanie Courtot, has developed a toolkit to help break down current barriers to accessing clinical and molecular data.

The FAIRplus consortium recently launched the FAIRification framework, an adaptable, easy-to-use guide for health and research organizations to make data more findable, accessible interoperable and reusable (FAIR).

“Data that can’t be found is data that can’t be reused,” said Courtot, who is Director of Genome Informatics and Principal Investigator at OICR, Assistant Professor of Medical Biophysics at the University of Toronto, and an author of the FAIRification framework. “The FAIRification framework provides practical, actionable steps for data owners to increase the value of their work and make their results available to the community.”

In addition to the framework, the consortium also created a FAIR ‘cookbook’ to support organizations in implementing FAIR principles. With the tools they created, the consortium has already applied the framework to clinical interventional study datasets, data generated in the lab, as well as real-world and clinical observational data.

Courtot’s involvement in the FAIRplus consortium began as part of her former role as Metadata Standards Coordinator for the European Bioinformatics Institute (EMBL-EBI), one of 21 partner organizations from academia and industry that contributed to the project.

She says using the framework to implement FAIR principles could help drive important innovations in health research and care.

“Standardized interoperable data benefits the global research community who can link different projects and outcomes, and ultimately benefits human health,” she says.

This story was adapted from an article by the European Bioinformatics Institute (EMBL-EBI).

Why some patients with a rare but deadly leukemia fare much better than others

Dr. Jaeseung Kim and colleagues have identified three subtypes of BCR-ABL1 acute lymphoblastic leukemia that respond very differently to targeted treatment.

There’s more to a rare type of leukemia than once thought, and new discoveries by OICR-supported researchers could bring about more personalized approaches to treat it.

For decades, scientists have known that two types of leukemia are driven by the ‘BCR-ABL1’ gene: chronic myelogenous leukemia (CML) and a more acute disease called BCR-ABL1 acute lymphoblastic leukemia (B-ALL). This knowledge helped generate a group of targeted drugs called tyrosine kinase inhibitors (TKIs) which have been very effective at treating CML, with most patients able to live a normal lifespan.

But patients with BCR-ABL1 B-ALL have had dramatically different outcomes with the same treatment. TKIs work very well for some and have little effect on others. About half of patients diagnosed with this type of leukemia die within five years of diagnosis, and there has been no clear reason why.

Dr. Jaeseung Kim and Dr. Faiyaz Notta have found a potential explanation and published it in a recent Nature Genetics paper.

Kim, Notta and colleagues used RNA sequencing to study samples of BCR-ABL1 B-ALL from 53 patients treated at University Health Network (UHN) in Toronto, hoping to understand how the disease’s molecular makeup impacted patients’ clinical outcomes. From that work, they identified three distinct subtypes of the disease that differed in their biology and response to treatment.

At the biological level, the subtypes are defined by how ‘mature’ blood cells were when they transformed into cancer, ranging from an early stage of maturation (“Early-Pro”) to mid stage (“Inter-Pro”) to late progenitor (“Late-Pro”). For patients, these subtypes translate to significantly different responses to TKIs. People with Early-Pro subtype had very poor outcomes, with high rates of relapse and a five-year overall survival rate of 33 per cent. Whereas people with Late-Pro subtype had markedly positive responses to treatment, with five year-overall survival at 73 per cent.

“This was traditionally thought of as a single disease,” says Kim, who started this research as a member of Dr. John McPherson’s lab at OICR and Dr. Notta’s lab at UHN and has since become a Laboratory Genetics and Genomics Fellow at Harvard Medical School. “Our study shows there are actually huge differences within this disease, and knowing which subtype a patient has could potentially influence how they are treated.”

If the findings from the study can be replicated and confirmed, Kim says they could one day be used to develop a classification tool that tells patients which subtype they have. Then, patients whose subtype has a poorer prognosis could be given more aggressive treatment earlier, giving them a better chance at fighting the disease. Findings from the study could also be used to develop drugs that specifically target the subtypes.

“This study addresses a longstanding question about this disease and how it responds to TKIs, and presents exciting new opportunities for how to treat it,” says Notta, an OICR Associate and Co-Lead of the PanCuRx Translational Research Initiative.

For Kim, one of the most encouraging aspects of the study is how effective treatment was for patients with the Late-Pro subtype.

“They had spectacular response,” he says. “If we can bring the other subtypes up to that same level of response, patients will be in a much better situation.”

New funding partnership with U of T Data Sciences Institute aims to drive new breakthroughs

Partnering with University of Toronto’s Data Sciences Institute (DSI) will give OICR researchers access to new funding and collaborations.

OICR is combining forces with another Ontario leader in data science research to help leverage Big Data into new discoveries about cancer.

OICR will be partnering with the Data Sciences Institute (DSI), University of Toronto’s hub for data science research and training.

“Partnering with DSI is a natural step for OICR, which has been a leading data science institute since its inception and has made major contributions in cancer data sharing and analysis,” says Dr. Lincoln Stein, Head of Adaptive Oncology for OICR and Professor of Molecular Genetics at the University of Toronto.

The partnership will allow OICR investigators and students to apply for DSI-sponsored training grants, take part in educational and network opportunities, find new collaborative opportunities and share expertise with other members of the institute.

“We are very excited to have the Ontario Institute for Cancer Research join our growing DSI community,” DSI Director Lisa Strug said in an announcement about the partnership. “By connecting and supporting data science researchers, the DSI advances research and nurtures the next generation of data- and computationally focused researchers.”

DSI faculty includes experts in various disciplines, from environmental sciences to economics, and Stein says adding OICR into the mix increases the chances of making new and exciting discoveries together.

“The greatest breakthroughs in science have come when members from different scientific disciplines meet, compare notes, and have an aha! moment,” Stein says.

OICR’s President and Scientific Director says collaborations like these ensure OICR remains at the forefront of cancer research and care.

“With a shared commitment to maximizing the health and economic benefit of our research for the people of Ontario, this partnership with DSI holds tremendous potential to drive breakthroughs in cancer research that can bring real benefits to those affected by cancer,” says OICR President and Scientific Director, Dr. Laszlo Radvanyi.

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