While the immune system is typically seen as key to fighting colds and infections, scientists are finding new and inventive ways to trigger the immune system to kill cancer cells.
One such strategy, known as ‘viral mimicry’, was previously discovered by a team of researchers at the Princess Margaret Cancer Centre led by Senior Scientist Dr. Daniel De Carvalho.
Now, recent findings from the same group, published in Nature, reveal a way to enhance the strategy to better target cancer cells.
Viral mimicry involves activating the production of double-stranded RNA (dsRNA) in the cell—a molecule that is typically found in viruses and is a ‘red flag’ that notifies the immune system of an infection. By producing dsRNA in cancer cells, the process mimics an infection and instructs the body to initiate an anticancer immune response.
Until now, the origin of immunogenic dsRNAs were unknown. In the current study, Dr. De Carvalho’s group found that ancient regions of DNA known as short interspersed nuclear elements (SINEs) are the source of these dsRNAs. Furthermore, certain drugs can specifically reactivate SINEs in cancer cells.
Discussing the role of SINEs in health, Dr. De Carvalho comments, “Humans acquired a series of ‘silent’ repetitive elements in our DNA over millions of years of evolution, but it has been unclear why or what purpose they serve. We set out to identify their function and have found that under the right conditions, they can be reactivated and stimulate our immune system.”
The current findings have added to this initial discovery by revealing the existence of a critical enzyme—known as ADAR1—that is used by cancer cells to evade the immune response induced by viral mimicry.
The study found that when cancer cells produce ADAR1, the dsRNA produced by the ancient DNA is disrupted. Furthermore, the research team showed that inhibiting ADAR1 made cancer cells more sensitive to drugs that induce viral mimicry.
“Since the ADAR1 activity is enzymatic, our work provides an exciting new target for drug development efforts and lays the foundation for the development of a completely new class of drugs that are able to exploit these ‘ancient weapons’ in our genome.” says Dr. De Carvalho.
This work was supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research, the São Paulo Research Foundation and The Princess Margaret Cancer Foundation. C O’Brien holds a Tier 2 Canada Research Chair in Translational Research in Colorectal Cancer and D De Carvalho holds a Tier 2 Canada Research Chair in Cancer Epigenetics and Epigenetic Therapy.
Mehdipour P, Marhon SA, Ettayebi I, Chakravarthy A, Hosseini A, Wang Y, de Castro FA, Yau HL, Ishak C, Abelson S, O’Brien CA, De Carvalho DD. Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency. Nature. 2020 Oct 21. doi: 10.1038/s41586-020-2844-1.
Princess Margaret Cancer Centre Senior Scientist Dr. John Dick has been elected to the prestigious National Academy of Medicine (NAM). The NAM is one of three academies that comprise the National Academies of Sciences, Engineering, and Medicine in the United States.
The Academy contains over 2,200 members who are recognized for their profound professional achievements in relation to health and medicine. Each year, the NAM elects up to 100 members, of whom 10 are selected from the international stage.
Dr. Dick is globally recognized for his discovery of leukemia stem cells, which was made possible by an assay he developed. The assay involves transplanting cells from either normal or cancer human adult bone marrow into an experimental model to gauge cancer initiation. Using this approach, he revealed that only a small subset of these cells were capable of initiating leukemia and were the main cause of disease relapse. These contributions shaped our understanding of cancer and revealed a new strategy for curing the disease.
Over his prolific career, Dr. Dick has published over 200 peer-reviewed articles, which have garnered over 55,000 citations. His landmark studies are routinely published in widely read scientific journals, including Nature, Science and Cell Stem Cell, and have revolutionized our understanding of leukemia and normal blood development.
The newly-elected class of 2020 was announced at the NAM annual meeting in October. Read more here.
Congratulations to Dr. Dick!
The UHN Office of Research Trainees (ORT) is proud to announce the release of the latest issue of The ORT Times!
The ORT Times is UHN's monthly trainee-focused newsletter. It highlights news and editorials about trainee life, articles to help developing researchers get the most out of their training experience at UHN, tips on career development, and research training opportunities within and outside of UHN.
Feature Stories:
PDF Appreciation Week
Read and download the full issue now!
To see past issues of The ORT Times, please visit ORT’s website.
One in five Canadian adults is currently living with arthritis, a disease-causing inflammation of the joints, which can result in chronic, debilitating pain, reduced mobility and premature disability. Arthritis is the leading cause of disability globally.
To address this growing crisis, the Schroeder Arthritis Institute, launched with a $25 million donation by philanthropists Walter and Maria Schroeder, will help UHN’s innovative arthritis program become a world-class hub for innovation in research, education and patient care.
Krembil Senior Scientists Dr. Robert Inman and Dr. Mohit Kapoor serve as Co-Directors of the Institute. Dr. Inman is a leader in field of ankylosing spondylitis and Dr. Kapoor’s research program is focused on advancing our understanding of osteoarthritis.
“Maria and I have put a great deal of thought into making this gift and ultimately we were persuaded by the vision and leadership of Dr. Kapoor and the arthritis team at UHN,” says Mr. Schroeder. “We want to be part of an effort that will finally put an end to unnecessary pain and suffering from arthritis and related conditions.”
Funds will go toward supporting top scientific talent and providing critical salary and infrastructure resources for the entire research team, which includes 51 scientists and clinician-scientists, 113 trainees and 200 staff.
The Institute will encompass research, education and innovations in clinical activities within four clinical programs: Hand, Orthopedics, Osteoporosis and Rheumatology, with the core goal of pushing the boundaries of discovery, learning and patient care.
The Institute builds on the momentum of the arthritis team’s progress in recent years, including innovations in surgical approaches for bone and joint diseases; new diagnostics and treatments in ankylosing spondylitis, lupus, osteoarthritis, osteoporosis, psoriatic arthritis, scleroderma and sjogren’s syndrome; as well as the development of predictive tools for orthopaedic surgery outcomes. This donation will extend these achievements by enabling the arthritis team to have global impact through the development of early diagnosis, innovative treatments and prevention.
“Our unique approach, creating alignment and synergy between our research and clinical teams, can only serve to help translate discoveries faster, and benefit patients sooner,” says Dr. Brad Wouters, Executive VP, Science & Research, at UHN. “This gift will help solidify UHN’s status as the largest research hospital in Canada and as a leader in arthritis research and clinical care, globally.”
To read more, click here.
A new cancer biotechnology company, TCRyption Inc., has been launched based on innovative findings from the Princess Margaret Cancer Centre (PM).
TCRyption Inc. emerges from the groundbreaking T-cell immunotherapy technologies created by PM Senior Scientist Dr. Naoto Hirano. The company was founded by Dr. Hirano along with pioneers of the T-cell and cancer fields, Drs. Tak Mak and Mark Davis.
The technology developed by Dr. Hirano belongs to a branch of cancer immunotherapy known as a T-cell receptor (TCR)-based adoptive cellular therapy which helps to stimulate the body’s own immune response to destroy cancer cells. Unfortunately, the effectiveness of this therapy is dependent on the HLA type of the patient (ie, the presence of certain immune molecules, of which there are many types that vary between patients). Due to this constraint, current therapies are generally effective for only a small patient group.
Dr. Hirano has overcome this problem through the development of a methodology that can generate an effective personalized therapeutic regimen for any patient’s HLA type regardless of its frequency—an innovation that will greatly expand treatment options and the groups of patients that can benefit from them.
"We are very pleased to announce the launch of TCRyption today; such innovative biotech partners embrace the power of immunity to fight cancer but also recognize that many current TCR-based applications will benefit only some patients. Our methodology at TCRyption allows us to bolster precision medicine for all patients and is an important part of helping us move forward together in our common goal to conquer cancer,” says Dr. Naoto Hirano.
With early support from the Princess Margaret Cancer Centre Innovation Acceleration Fund for developing the technology, company creation activities were led by UHN’s Technology Development & Commercialization team (TDC) and TIO Bioventures with an initial $10 million in seed financing to advance the innovation so that it can help patients.
“We are thrilled to have TCRyption launched with the core facilities located right here in Toronto with some of the biggest names and pioneers in cancer immunology as part of the team,” says Mark Taylor, Director of UHN’s TDC.
To learn more about TCRyption Inc., please view the news release here. To read about recent and related findings from Dr. Hirano, published in the journal eLife, click here.
UHN has a rich history of research firsts that have revolutionized medicine and health care. Last month, Princess Margaret Cancer Centre scientists Drs. M. Vera Peters, James Till and Ernest McCulloch were among six Canadian physicians and researchers recognized with Canada Post’s stamp issue titled Medical Groundbreakers.
The stamp issue, which also commemorates Drs. Bruce Chown, Julio Montaner and Balfour Mount, was proposed to Canada Post by UHN’s Dr. Jean Wang, a Clinician Scientist at Princess Margaret Cancer Centre and a member of the Canada Post Stamp Advisory Committee.
“All of these physicians and researchers changed the face of health care in Canada and globally,” says Dr. Wang. “Along with the beautiful stamp designs, we want to share with Canadians the stories behind these remarkable individuals and their achievements.”
As one of only ten women in her medical school graduating class of 1934, Dr. M Vera Peters persisted through barriers and criticism to revolutionize cancer treatment. Dr. Peters discovered that radiation could cure Hodgkin lymphoma, a cancer previously thought to be incurable, and later observed that radiation in conjunction with breast-conserving lumpectomies was effective for treating early-stage breast cancer, sparing many women from radical mastectomies.
In a landmark study looking at the effects of radiation on bone marrow, Drs. James Till and Ernest McCulloch identified blood-forming stem cells—a discovery that laid the foundation for stem cell science and explained the basis of bone marrow transplants for treating blood cancers. Stem cell research has paved the way for regenerative medicine and the development of potential stem cell-based treatments for diseases such as diabetes, multiple sclerosis and Parkinson disease.
Dr. Wang reflects, “There could not be a better time to share these stories with Canadians. Through these stamps we salute all health care professionals who devote their lives and their work to our well-being.”
With the global COVID-19 crisis, we have seen a surge of misinformation and baseless claims falsely associated with many leading health-care institutions worldwide. Unfortunately, external users have been receiving phishing emails claiming to be from the UHN Research domain. These emails do not originate from UHN Research or any affiliated parties.
To raise awareness about this issue, and to coincide with Cyber Security Awareness Month, research at UHN has launched a phishing education webpage for external users.
Visit the site by clicking on the following link: Protect Yourself from Spam & Phishing
Note that the spam and phishing awareness web page is relevant for individuals who do not work at UHN and appear to be receiving spam from uhnresearch.ca. If UHN patients, volunteers or collaborators are receiving spam emails, they are encouraged to contact UHN Digital through internal routes.
We are actively working to better understand how our domain names are being misused and to secure our domain name so we can halt these emails at their source. UHN Digital is working to centralize our outbound mail channels and publish domain reputation information that will allow internet service providers to differentiate legitimate emails from spam emails.
As a not-for-profit public hospital, UHN never sends unsolicited emails or advertises products or services to patients or the general public. By providing users with tools to help spot phishing emails, we hope to empower users to safeguard their personal information from fraudsters.
Research conducted at UHN's research institutes spans the full spectrum of diseases and disciplines, including cancer, cardiovascular sciences, transplantation, neural and sensory sciences, musculoskeletal health, rehabilitation sciences, and community and population health.
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