December 2, 2020
Researchers at the University of Guelph and McMaster University create combination immunotherapy approach to treat breast tumours and other cancers
Over the last few decades, scientists have made significant progress in harnessing the immune system to treat cancers. Despite these advances, many types of cancer can still evade the immune system and current immunotherapies. Dr. Sam Workenhe is developing better treatment options for patients with these hard-to-treat diseases.
In his recent study, published in Nature Communications Biology, Workenhe and collaborators at the University of Guelph and McMaster University discovered a new combination immunotherapy approach for breast tumours and other cancers. Their approach leverages cancer-killing viruses, called oncolytic viruses, and chemotherapy to trigger tumour inflammation, stimulating the body’s immune system to control tumour growth. Their combination leveraged the oncolytic virus, oHSV-1, and the chemotherapy agent, Mitomycin-C.
The research team demonstrated the effectiveness of this treatment approach in mouse models of breast cancer. They found that that mice treated with this combination therapy lived approximately two months longer than untreated ones – a significant difference relative to the short lifespan of these mouse models.
“Simply put, we wake up the immune system,” says Workenhe, Assistant Professor at the University of Guelph’s Ontario Veterinary College and an OICR Joseph and Wolf Lebovic Fellowship Program awardee. “Our study proves that aggressive tumours without immune cells can be made to render an immune response. Understanding how to design treatments that can potentially activate the immune system against cancer can revolutionize the current standards of care.”
Additionally, the study delineated the anticancer mechanisms of their approach, detailing how each element kickstarts an immune response against the tumours. Workenhe, who is a trained veterinarian and a virologist, is now applying these findings to further study immune responses and inflammatory cell death in tumours.
“A lot of people are excited about engineering viruses to inflame the tumour and improve cancer treatment,” says Workenhe. “The implications of these findings for human cancer therapy may be huge.”
This post was adapted from a University of Guelph news story.
November 18, 2019
McMaster University researchers validate a new treatment approach that could help bring the benefits of Adoptive T-cell therapies to patients with solid tumours
Adoptive T-cell therapy (ACT) is an emerging form of immunotherapy that uses a patient’s own re-engineered immune cells to eliminate their cancer. Although ACT is effective against specific types of cancer, like certain blood cancers, these therapies are ineffective against the majority of common tumours.
Researchers at McMaster University are developing a new combination approach that could overcome the limitations of current ACT, and bring the benefits of this promising therapy to many more patients.
The approach, as recently described in The Journal of Clinical Investigation, combines ACT with specially-designed vaccines, called oncolytic virus vaccines (OVVs), to bring about the complete destruction of a solid tumour.
Dr. Scott Walsh, Postdoctoral Fellow in Dr. Yonghong Wan’s lab at McMaster University and first author of the publication, describes the “push and pull” mechanism behind their combination approach.
“We found that oncolytic viruses could stimulate the implanted T-cells to proliferate. In other words, they could push the cancer-fighting cells to multiply,” says Walsh. “Then we found that these viruses could also pull the cancer-fighting T-cells into the core of the tumour, which simply could not be done with ACT alone.”
In this study, the research group discovered that their ACT/OVV combination approach could engage the entire immune system to eliminate solid tumours and generate a long-term tumour-resisting effect in experimental animal models. Whereas current ACT can only kill specific tumour cells, their approach was effective at eliminating the various types of cells within solid tumours.
“Usually, ACT can only target the tumour cells that have a specific set of molecular markers. This is a problem because tumours can often shed these marked cells and return with a vengeance,” Walsh says. “Our approach engages the immune system as a whole, not just the re-engineered cells, to eliminate a broader variety of tumour cells and prevent the tumour from coming back over the long term.”
To bring this new approach into the next stage of development, the study group teamed up with experts across the province through OICR’s Immuno-oncology Translational Research Initiative. The team includes researchers with deep immuno-oncology expertise and extensive commercialization experience.
“Bringing this idea into the next stage of development requires collaboration across areas of expertise,” says Walsh, who holds a patent on the combination approach. “We’re looking forward to building on our past successes and using our collective expertise to move into more advanced animal models, and then onto clinical trials.”
September 30, 2019
McMaster University researcher and OICR Investigator, Dr. Kristin Hope, turns her stem cell discovery into a new treatment approach for leukemia.
A few years ago, Dr. Kristin Hope and her research team discovered a new way to grow rare life-saving blood stem cells. Now, the Hope Lab is using this discovery to suppress leukemic stem cells – the cells at the “root” of leukemia.
In their most recent study, published earlier this month in Cancer Research, the Hope Lab discovered that the same molecular pathway they found previously could be turned off to grow healthy stem cells could be turned on to impair the development of cancer stem cells.
The study suggests that this pathway, called the aryl hydrocarbon receptor (AHR) signaling pathway, could be leveraged as a potential therapeutic approach for acute myeloid leukemia – one of the most common subtypes of leukemia.
“We saw a loss of leukemic stem cells by activating – or turning on – the AHR pathway,” Hope says. “This brings us a step closer to a potential new therapy for patients with leukemia.”
The study group used a small molecule to activate the AHR pathway, finding that it had a significant effect in eliminating leukemic stem cells, but no effect on healthy cells. The group found similar results in cell cultures as well as in mice that were transplanted with human leukemia cells.
Hope, who is a Principal Investigator at McMaster University’s Stem Cell and Cancer Research Institute, will continue investigating this small molecule as a potential drug that could complement chemotherapies in the future.
“We will continue building on our understanding of the AHR pathway and how to control it,” she says. “This understanding will help us in the development of new therapies so that our discoveries can one day help patients.”
September 10, 2018
Hamilton researchers discover that cancer stem cells may not be the only culprits of acute myeloid leukemia relapse
Although current chemotherapy for acute myeloid leukemia (AML) is effective in the short term, the disease often returns a few years after treatment. A new study suggests that the relapse of leukemia may not be caused by leukemic stem cells – a special set of cells that can avoid initial treatment by not dividing, then give rise to new cancerous cells after therapy – but rather a different class of leukemic cells.
April 9, 2018
Dr. Gregory Pond, Jenna Sykes, Dr. Richard Cook, Yonathan Brhane, Dr. Wei Xu.
Cancer researchers often confront quantitative challenges and puzzles that are best addressed by biostatisticians – specialists in a field for which there is a growing demand. In a 2008 survey of Ontario oncologists, eight in 10 respondents identified the lack of trained biostatisticians as a factor limiting their progress in cancer research. OICR has recently renewed funding for the Biostatistics Training Initiative (BTI) following a successful review. With this funding, the BTI will continue to benefit Ontario’s cancer research community and develop the next generation of cancer biostatisticians. The BTI is run in partnership with in the University of Waterloo and McMaster University.
December 4, 2017
OICR launches groundbreaking Cancer Therapeutics Innovation Pipeline to drive cutting-edge therapies to the clinic
Ten new projects were selected in the pipeline’s inaugural funding round, highlighting Ontario’s strengths in collaboration and drug discovery.
Toronto (December 4, 2017) – The Ontario Institute for Cancer Research (OICR) today announced the Cancer Therapeutics Innovation Pipeline (CTIP) initiative and the first 10 projects selected in CTIP’s inaugural round of funding. CTIP aims to support the local translation of Ontario discoveries into therapies with the potential for improving the lives of cancer patients. The funding will create a new pipeline of promising drugs in development, and attract the partnerships and investment to the province necessary for further clinical development and testing.
“Ontario congratulates OICR on this innovative approach to driving the development of new cancer therapies,” says Reza Moridi, Ontario’s Minister of Research, Innovation and Science. “The Cancer Therapeutics Innovation Pipeline will help ensure that promising discoveries get the support they need to move from lab bench to commercialization, and get to patients faster.”
October 24, 2017
Brain tumours resulting from the spread of cancer from its primary location, known as brain metastases (BM), are the most common form of brain tumours in adults. A team of Ontario-based researchers recently identified two genes that seem to play a central role in BM in lung cancer patients – findings that could lead to improved biomarkers and treatments for BM.
In a study published in the journal Acta Neuropatologica, Mohini Singh and her collaborators focused on a class of cells they have termed Brain Metastases Initiating Cells (BMICs), which leave the primary site of cancer and migrate to the brain.
Singh, a biochemistry PhD candidate in the lab of Dr. Sheila Singh at McMaster University, explains the approach the team took to study these cells. “There was a lack of preclinical models that we could use to comprehensively study BMICs and understand the mechanisms behind them. To conduct our study we used brain metastases from lung cancer patients, which we cultured in conditions to enrich for BMICs, and then transplanted them into mice. This method allowed us to study BMICs within a living host, which provides a more accurate representation of the development of brain metastasis in humans.”
The researchers performed in vitro and in vivo RNA interference screens utilizing their unique BM models, and found two genes that were essential to the regulation of BMICs: SPOCK1 and TWIST2. “We discovered that SPOCK1 is a regulator of self-renewal in BMICs, playing a role in the initiation of lung tumours and their metastasis to the brain,” explains Singh. Furthermore, the results were clinically relevant. “Increased SPOCK1 expression was seen in lung cancer biopsies of patients with known brain metastases, and was correlated with poor survival.” Through protein-protein interaction mapping the researchers also identified new pathway interactors of the two genes that could be used as novel targets in treatment of BM in lung cancer patients.
“Identifying these two genes could be of great use in improving the treatment of lung cancer. In the future we could predict those patients who are most at risk of developing a brain metastasis and use drugs to target BMIC regulatory genes such as SPOCK1 and TWIST2 to destroy the initiating cells and to block the spread,” says Singh. “This would result in keeping the lung cancer locally controlled and therefore more treatable.”
OICR funding was used to establish this study with further significant funding coming from the Canadian Cancer Society and the Brain Canada Studentship.
October 20, 2017
Researchers have discovered a new potential treatment for acute myeloid leukemia (AML). They found that boosting fat cells (adipocytes) within bone marrow with the use of a common diabetes drug slowed the growth of cancerous cells and promoted the regeneration of healthy blood cells.
October 11, 2017
Partners congratulate Turnstone Biologics
Canadian academic institutions and research organizations are congratulating Turnstone Biologics on a new partnership with AbbVie to develop cancer-fighting viruses (also called oncolytic viral immunotherapies).
Turnstone was founded in Ottawa based on research led by Dr. John Bell (from The Ottawa Hospital and uOttawa), Dr. Brian Lichty (from McMaster University) and Dr. David Stojdl (from the Children’s Hospital of Eastern Ontario and uOttawa). The Ontario Institute for Cancer Research (OICR) and BioCanRx have also played a key role in advancing the technology.
Quick Facts and Links
- Turnstone was recently recognized as one of the top 15 biotech start-ups in the world.
- In 2016, Turnstone secured US$41 million in venture capital (VC) funding. This is believed to be the largest VC deal in Ottawa since 2013 and the second largest biotech VC deal in Canada in 2016.
- As of October 2017, Turnstone had 25 employees in Ottawa, Hamilton and New York. It expects to approximately double its employees by the end of next year.
- Turnstone’s most advanced product is called Ad-MG1-MAGEA3. It is produced in The Ottawa Hospital’s Biotherapeutics Manufacturing Centre and the McMaster Immunology Research Centre.
- Top journal Science called cancer immunotherapy the “breakthrough of the year” in 2013.
- Ad-MG1-MAGEA3 is currently being tested in clinical trials at several hospitals across Canada. People who are interested in participating in these trials can read these frequently asked questions.
- While public funding is crucial for cancer research discoveries, private investment is almost always necessary to advance the development of new therapies, as this can cost more than US$2.5 billion.
- Turnstone was co-founded by FACIT, The Ontario Institute for Cancer Research’s commercialization partner, which provided initial management, seed financing, intellectual property consolidation and hiring of initial employees including the CEO.
- Numerous organizations have supported the research team, including the Alliance for Cancer Gene Therapy, Angels of Hope, BioCanRx, the Canada Foundation for Innovation, the Canadian Cancer Society Research Institute, the Canadian Institutes of Health Research, CHEO Foundation, Hair Donation Ottawa, the Ontario Institute for Cancer Research, the Ontario Ministry of Research, Innovation and Science, The Ottawa Hospital Foundation, the Ottawa Regional Cancer Foundation and the Terry Fox Research Institute.
August 17, 2017
Research from McMaster University has identified new regulators of brain metastases in patients with lung cancer.
These regulators are the genes called SPOCK1 and TWIST2.
July 4, 2016
OICR congratulates Drs. Mark Levine, Eduardo L. Franco and Gerald Batist, new recipients of the Order of Canada
Three cancer researchers were invested into the Order of Canada over the weekend, including Dr. Mark Levine, C.M., who was honoured for his contributions as an oncologist, researcher and clinician and because he has developed several new treatments for cancer patients that are now used as standard of practice in Canada.
Levine is Director of the Ontario Clinical Oncology Group (OCOG), Chair of the Department of Oncology for the Michael G. DeGroote School of Medicine at McMaster University and a medical oncologist at Juravinski Cancer Centre at Hamilton Health Sciences.
June 1, 2016
Research supported by the Movember Foundation, the Ontario Institute for Cancer Research and Prostate Cancer Canada
Toronto, ON – June 1, 2016 – The Movember Foundation, the Ontario Institute for Cancer Research (OICR) and Prostate Cancer Canada today announced $3 million in funding for a new Phase III clinical trial to evaluate if magnetic resonance imaging (MRI) can replace the current standard of care to diagnose prostate cancer. The primary objective of the multi-centre trial, called PRECISE, is to determine whether MRI imaging can spare some men from undergoing a biopsy and avoid the possible associated side effects.
The trial will be led by Dr. Laurence Klotz of the Sunnybrook Research Institute in Toronto, a world leader in the field of prostate cancer research and in the global adoption of active surveillance, a standard practice to monitor patients with low risk prostate cancer.