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.
July 8, 2020
Protecting cancer patients from COVID-19: world-first clinical trial tests a novel immune-boosting strategy
In the race to find new ways to prevent and treat COVID-19, OICR-supported researchers have launched an innovative clinical trial focussed on strengthening the immune system for one of the most vulnerable populations – cancer patients.
The trial involves IMM-101, a preparation of safe, heat-killed bacteria that broadly stimulates the innate, or “first-response,” arm of the immune system. The researchers hope that boosting cancer patients’ immune systems with IMM-101 will protect them from developing severe COVID-19 and other dangerous lung infections.
Researchers from The Ottawa Hospital came up with the idea for the trial and worked with the Canadian Cancer Trials Group (CCTG) at Queen’s University to design and run it in centres across the country. Funding and in-kind support, valued at $2.8 million, is being provided by the Canadian Cancer Society, BioCanRx, the Ontario Institute for Cancer Research, The Ottawa Hospital Foundation, The Ottawa Hospital Academic Medical Organization, ATGen Canada/NKMax, and Immodulon Therapeutics, the manufacturer of IMM-101.
“An effective vaccine that provides specific protection against COVID-19 could take another year or more to develop, test, and implement,” says Dr. Rebecca Auer, study lead, surgical oncologist and Director of Cancer Research at The Ottawa Hospital and associate professor at the University of Ottawa. “In the meantime, there is an urgent need to protect people with cancer from severe COVID-19 infection, and we think this immune stimulator, IMM-101, may be able to do this.”
“This trial could support an important change to the standard of care for cancer patients by administration of IMM-101 prior to starting cancer treatment,” says Dr. John Bell, Senior Scientist at the Ottawa Hospital Research Institute, Scientific Director of BioCanRx and co-lead of OICR’s Immuno-oncology Translational Research Intitiative. “Accelerating to the clinic, biotherapeutics that can enhance the quality of life of those living with cancer.”
The trial, called CCTG IC.8, has been approved by Health Canada and is expected to open at cancer centres across Canada this summer. People who are interested in participating should speak with their cancer specialist.
“OICR is excited to be collaborating on such a landmark clinical trial supporting cancer patients in this unprecedented time,” says Dr. Laszlo Radvanyi, President and Scientific Director, OICR. “IMM-101 may be an effective approach to protect our vulnerable patients not only against COVID-19, but also to boost their immune system to fight cancer.”
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.”
October 4, 2019
OICR is proud to announce two new partnerships between research trainees in Ontario and collaborators in Israel, supported by Joseph and Wolf Lebovic.
The Joseph and Wolf Lebovic Fellowship Program, a joint initiative between the Hebrew University of Jerusalem’s Institute for Medical Research Israel-Canada (IMRIC) and OICR, is supporting two new partnerships between local cancer researchers and those in Israel.
This is the second round of this fellowship program that aims to strengthen collaboration across the two countries by pairing trainees in complementary areas of expertise. Both projects focus on the interaction between tumours and the immune system to develop new and more effective therapeutic strategies for cancer.
Over the next two years, the new fellows will develop their mutually-beneficial partnerships, allowing them to further their research while building their collaboration skills.
“We are investing in talented trainees with the potential to make a significant impact in cancer research, while fostering international collaboration,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “We cannot wait to see what they will accomplish in the years to come.”
Teaming up to take on a new approach
Principal Investigator in Israel: Dr. Lior Nissim, Assistant Professor at IMRIC
Fellow: Natella Buketov, Master of Science student at IMRIC
Principal Investigator in Ontario: Dr. Samuel Workenhe, Assistant Professor at McMaster University
Fellow: Jeffrey Wei, Master of Science student at McMaster University
Developing viruses that alarm the immune system to fight against cancer is a sought after goal around the world. A common challenge with this approach is that cancer cells can often “shut off” or silence these alarms, and thus, the cancer cells remain undetectable to the immune system.
Workenhe and Nissim hypothesize that synthetic molecules – sequences of DNA that cannot be found in nature – could be used to overcome this challenge and effectively trigger an immune response against cancer cells.
Through the Lebovic Fellowship, these two research groups have teamed up to explore the possibility of using viruses, developed by the Workenhe Lab, to deliver synthetic molecules, developed by the Nissim Lab, to cancer cells. Over the next two years, they will work to optimize their platforms, develop the viruses and test them in infected cell cultures and tumour-bearing mice.
“There’s a lot of drive behind this project,” says Workenhe. “We both want to find a way to make this work and overcome the challenges of viral immunotherapies together.”
Partnering to accelerate research
Principal Investigator in Israel: Dr. Sheera Adar, Senior Lecturer at IMRIC
Fellow: Dr. Pooja Chauhan, Postdoctoral Fellow at IMRIC
Principal Investigator in Ontario: Dr. Carolina Ilkow, Scientist at the Ottawa Hospital Research Institute and Assistant Professor at the University of Ottawa
Fellow: Emily Brown, Master of Science student at Ottawa Hospital Research Institute and the University of Ottawa
The Adar Lab and the Ilkow Lab are both interested in the SWI/SNF complex – a cellular machine that affects how our DNA is packaged and coiled.
The Adar Lab is working to better understand how SWI/SNF affects DNA damage repair in cancer cells. The Ilkow Lab is working to better understand how SWI/SNF can be altered to improve immunotherapies. They recognized that they can study SWI/SNF better together.
With the support of the Lebovic Fellowship, these groups are partnering to investigate SWI/SNF with two different approaches while sharing common methods, resources and expertise. By doing so, the researchers expect to reduce duplicative efforts and accelerate both projects. “I’m excited to be involved in the field of cancer immunotherapy,” says Brown. “Seeing that your work has direct impact is really rewarding, and I’m excited to help contribute to such an innovative approach.”
July 3, 2019
Bridges built between Israel and Canada thanks to philanthropic donation from Joseph and Wolf Lebovic
TORONTO (July 3, 2019) – The Ontario Institute for Cancer Research (OICR), the Institute for Medical Research Israel-Canada (IMRIC) at the Hebrew University of Jerusalem and the Canadian Friends of Hebrew University (CFHU) today honour the successful conclusion of the first round of the Joseph and Wolf Lebovic Cancer Genomics and Immunity Fellowship Program, a cross-continent multidisciplinary collaboration between experts in cancer research. The Program forged two new partnerships between labs in Canada and Israel and provided a unique training opportunity for early career researchers in both countries. These collaborations led to the development of a new potential cancer-killing virus and a new drug candidate for leukemia.
Fellowships were awarded to Adrian Pelin from the lab of Dr. John Bell at The Ottawa Hospital Research Institute, in Ottawa, Ontario and Yoav Charpak Amikam from the lab of Dr. Ofer Mandelboim at IMRIC in Jerusalem, Israel. The collaboration improved the specificity and immune-triggering abilities of the potential oncolytic Vaccinia virus.
Another pair of fellowships were awarded to Dr. Laura Garcia-Prat from the lab of Dr. John Dick at the Princess Margaret Cancer Centre, in Toronto, Ontario and Waleed Minzel and Eric Hung from the lab of Dr. Yinon Ben-Neriah at IMRIC. This partnership enabled the development of leukemia xenograft models to help validate the efficacy of a new drug candidate, as recently published in the scientific journal Cell.
The Lebovic Fellowship Program was established by a philanthropic donation provided to IMRIC by Joseph and Wolf Lebovic – two brothers who survived the Holocaust, immigrated to Canada and have recently been appointed as Members of the Order of Canada for their contributions to the Toronto community.
“We’d like to congratulate the fellows today on their progress which was made possible by the generous support of Joseph and Wolf Lebovic. The funding provided by the Lebovic brothers allowed us to create a platform for Ontario scientists to establish collaborations with researchers in Israel and we look forward to strengthening this platform for future collaborative work,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR.
“We congratulate the fellows today on their achievements during this first round of the program. IMRIC is proud to continue our collaboration with an institute as distinguished as OICR, supported by the inspiring philanthropy of Joseph and Wolf Lebovic,” says Prof. Haya Lorberboum-Galski, Chairman of IMRIC. “We feel that this collaboration between top Canadian and Israeli researchers will surely lead to significant and game-changing advances in the world arena.”
“Thanks to the vision and generosity of Joseph and Wolf Lebovic, they have been instrumental in creating an international collaboration that will continue to strengthen Israel-Canada connections while benefitting humankind,” says Rami Kleinmann, CEO and President of Canadian Friends of Hebrew University. “CFHU is grateful for their continuing and dedicated support.”Continue reading – Bridges built between Israel and Canada thanks to philanthropic donation from Joseph and Wolf Lebovic
May 21, 2019
Dr. Brigitte Thériault, a Senior Research Scientist at OICR, discusses the work of the Drug Discovery team to develop new drugs that awaken the body’s immune system to recognize and attack cancer cells.
November 8, 2018
Dr. Daniel De Carvalho discusses his study published in Nature Communications, which found a gene signature biomarker that may help predict which patients will respond to immune therapy.
November 6, 2018
Researchers studying ovarian cancer identify adapter protein 3BP2 as a key component of immune system function and a powerful tool that could be used to activate the immune system against hidden tumour cells.
August 16, 2018
Ottawa researchers discover a new way to make cancer cells more susceptible to virus-based therapies
Over the past decade, researchers have made significant progress in designing oncolytic viruses (OVs) – viruses that destroy cancer cells while leaving healthy tissue unharmed. However, some cancer cells are resistant to this type of therapy and their resistance mechanisms remain poorly understood.
Researchers at the The Ottawa Hospital and University of Ottawa, under the leadership of Dr. Carolina Ilkow, have discovered that a common cellular mechanism, RNAi, allows cancer cells to fight back against cancer-fighting viruses. Their findings, recently published in the Journal for Immunotherapy of Cancer, show that blocking RNAi processes in tumours can make cancer cells more susceptible to OVs.
July 27, 2018
Over the past decade, OICR’s laboratories have procured state-of-the-art equipment and developed leading-edge technologies to help answer pressing cancer research questions. The effective and proper use of advanced laboratory tools is dependent on specialized knowledge and skills on the part of the operator. OICR’s platform for laboratory training, BioLab, is ensuring that Ontario’s cancer researchers have the knowledge they need to explore the full potential of some of the province’s most advanced cancer research equipment.
June 14, 2018
New OICR President and Scientific Director comments on breakthrough in breast cancer T-cell immunotherapy
For the first time, a patient’s late-stage breast cancer has been successfully treated with T-cell immunotherapy. This cutting-edge approach, which is currently in clinical trials in the U.S., modified the patient’s naturally-occurring immune cells to fight her tumours that had spread throughout her body. The patient has been cancer free for the past two years and her remarkable tumour regression represents the potential impact of this new immunotherapeutic approach.
June 13, 2018
Some common pathogens, like the Epstein-Barr virus (EBV), can turn healthy cells into cancer cells, but it is not well understood how they do so. Better understanding how such pathogens work allows researchers to find new ways to target the pathogen’s disease-causing mechanisms and ultimately find new treatments for certain virus-induced cancers.
Dr. Ivan Borozan, from Dr. Vincent Ferretti’s Lab at OICR, and Prof. Lori Frappier at the University of Toronto are working together to better understand EBV and how it triggers the transformation of normal cells to cancerous cells, also known as oncogenesis. Together, they have identified that a key protein expressed by EBV, BKRF4, is one of the likely drivers behind EBV-induced stomach cancers.