Researchers at Cardiff University have discovered a new type of killer T-cell that offers hope of a “one-size-fits-all” cancer therapy.
T-cell therapies for cancer—where immune cells are removed, modified and returned to the patient’s blood to seek and destroy cancer cells—are the latest paradigm in cancer treatments.
The most widely-used therapy, known as CAR-T, is personalized to each patient, but it only targets a few types of cancers and has not been successful for solid tumors, which make up the vast majority of cancers.
Cardiff researchers have now discovered T-cells equipped with a new type of T-cell receptor (TCR) which recognizes and kills most human cancer types, while ignoring healthy cells.
This TCR recognizes a molecule present on the surface of a wide range of cancer cells as well as in many of the body’s normal cells but, remarkably, is able to distinguish between healthy cells and cancerous ones, killing only the latter.
The researchers said this meant it offered “exciting opportunities for pan-cancer, pan-population” immunotherapies not previously thought possible.
How does this new TCR work?
Conventional T-cells scan the surface of other cells to find anomalies and eliminate cancerous cells—which express abnormal proteins—but ignore cells that contain only “normal” proteins.
The scanning system recognizes small parts of cellular proteins that are bound to cell-surface molecules called human leukocyte antigen (HLA), allowing killer T-cells to see what’s occurring inside cells by scanning their surface.
HLA varies widely between individuals, which has previously prevented scientists from creating a single T-cell-based treatment that targets most cancers in all people.
But the Cardiff study, published this week in Nature Immunology, describes a unique TCR that can recognize many types of cancer via a single HLA-like molecule called MR1.
Unlike HLA, MR1 does not vary in the human population—meaning it is a hugely attractive new target for immunotherapies.
What did the researchers show?
T-cells equipped with the new TCR were shown, in the lab, to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells, while ignoring healthy cells.
To test the therapeutic potential of these cells in vivo, the researchers injected T-cells able to recognize MR1 into mice bearing human cancer and with a human immune system.
This showed “encouraging” cancer-clearing results which the researchers said was comparable to the now NHS-approved CAR-T therapy in a similar animal model.
The Cardiff group were further able to show that T-cells of melanoma patients modified to express this new TCR could destroy not only the patient’s own cancer cells, but also other patients’ cancer cells in the laboratory, regardless of the patient’s HLA type.
Professor Andrew Sewell, lead author on the study and an expert in T-cells from Cardiff University’s School of Medicine, said it was “highly unusual” to find a TCR with such broad cancer specificity and this raised the prospect of “universal” cancer therapy.
“We hope this new TCR may provide us with a different route to target and destroy a wide range of cancers in all individuals,” he said.
“Current TCR-based therapies can only be used in a minority of patients with a minority of cancers.
“Cancer-targeting via MR1-restricted T-cells is an exciting new frontier – it raises the prospect of a ‘one-size-fits-all’ cancer treatment; a single type of T-cell that could be capable of destroying many different types of cancers across the population.
“Previously nobody believed this could be possible.”
What happens next?
Experiments are under way to determine the precise molecular mechanism by which the new TCR distinguishes between healthy cells and cancer.
The researchers believe it may work by sensing changes in cellular metabolism which causes different metabolic intermediates to be presented at the cancer cell surface by MR1.
The Cardiff group hope to trial this new approach in patients towards the end of this year following further safety testing.
Professor Sewell said a vital aspect of this ongoing safety testing was to further ensure killer T-cells modified with the new TCR recognize cancer cells only.
“There are plenty of hurdles to overcome however if this testing is successful, then I would hope this new treatment could be in use in patients in a few years’ time,” he said.
Professor Oliver Ottmann, Cardiff University’s Head of Haematology, whose department delivers CAR-T therapy, said: “This new type of T-cell therapy has enormous potential to overcome current limitations of CAR-T, which has been struggling to identify suitable and safe targets for more than a few cancer types.”
Professor Awen Gallimore, of the University’s division of infection and immunity and cancer immunology lead for the Wales Cancer Research Centre, said: “If this transformative new finding holds up, it will lay the foundation for a ‘universal’ T-cell medicine, mitigating against the tremendous costs associated with the identification, generation and manufacture of personalized T-cells.
“This is truly exciting and potentially a great step forward for the accessibility of cancer immunotherapy.”
Reprinted from Cardiff University
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Another presumptive case of COVID-19 confirmed in Toronto | News – Daily Hive
Ontario health officials announced a fourth presumptive case of the novel coronavirus in the province Sunday, bringing the total number of cases Canada has seen to 10.
The latest patient is a woman who arrived in Canada from China on February 21. That same day, she followed advice from Telehealth Ontario and went to North York General Hospital because she had an intermittent cough.
Her illness was mild, and after being tested for COVID-19 she was discharged and is now self-isolated at home.
Ontario’s lab returned a presumptive positive test for the virus Sunday, and further testing will be done at the national lab in Winnipeg to confirm that result.
“Because of all the proper protocols and procedures that are in place to contain this virus and exposure to others was limited, I want to assure the public that the risk to Ontarians remains low,” said Dr. David Williams, Ontario’s Chief Medical Officer of Health.
The woman wore a mask on her flight back to Toronto, and has not been in touch with many people since she returned.
Right now, this woman is the only known active case of COVID-19 in Ontario. The first three patients who all returned from China earlier this year have recovered and cleared the virus from their bodies.
[Wuhan Woman With No Coronavirus Symptoms Infects 5 Relatives Revealing New Extent of Challenge] – Mash Viral
China: A 20-year-old Chinese woman from Wuhan, the epicenter of the coronavirus outbreak, traveled 400 miles(675 km) north to Anyang where she infected five relatives, without ever showing signs of infection, Chinese scientists reported on Friday, offering new evidence that the virus can be spread asymptomatically.
The case study, published in the Journal of the American Medical Association, offered clues about how the coronavirus is spreading, and suggested why it may be difficult to stop.
“Scientists have been asking if you can have this infection and not be ill? The answer is apparently, yes,” said Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical Center, who was not involved in the study.
China has reported a total of 75,567 cases of the virus known as COVID-19 to the World Health Organization (WHO) including 2,239 deaths, and the virus has already spread to 26 countries and territories outside of mainland China.
Researchers have reported sporadic accounts of individuals without any symptoms spreading the virus. What’s different in this study is that it offers a natural lab experiment of sorts, Schaffner said.
“You had this patient from Wuhan where the virus is, traveling to where the virus wasn’t. She remained asymptomatic and infected a bunch of family members and you had a group of physicians who immediately seized on the moment and tested everyone.”
According to the report by Dr. Meiyun Wang of the People’s Hospital of Zhengzhou University and colleagues, the woman traveled from Wuhan to Anyang on January 10 and visited several relatives. When they started getting sick, doctors isolated the woman and tested her for coronavirus. Initially, the young woman tested negative for the virus, but a follow-up test was positive.
All five of her relatives developed COVID-19 pneumonia, but as of February 11, the young woman still had not developed any symptoms, her chest CT remained normal and she had no fever, stomach or respiratory symptoms, such as cough or sore throat.
Scientists in the study said if the findings are replicated, “the prevention of COVID-19 infection could prove challenging.”
Key questions now, Schaffner said, are how often does this kind of transmission occur and when during the asymptomatic period does a person test positive for the virus.
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SARS lessons help Canada prep for COVID-19, but hospital capacity a worry – Nanaimo News Bulletin
Canadian medical experts say the country’s already overstretched emergency rooms would find it difficult to cope if a true outbreak of the novel coronavirus, or COVID-19, were to take hold in Canada.
So far, the virus has been relatively contained to mainland China, thanks in part to one of the largest quarantines in modern history.
“We must not look back and regret that we failed to take advantage of the window of opportunity that we have now,” Dr. Tedros Adhanom Ghebreyesus, director general of the World Health Organization, said in a message to all the world’s countries Friday.
The risk of contracting the virus in Canada right now is extremely low, and public health officials have been lauded for their efforts to detect and isolate the nine cases confirmed in the country so far.
The hundreds of patients across the country who have tested negative for the virus are also a sign that containment efforts are working as they should.
But Canada’s most recent case in British Columbia has raised fears about where and how the disease is being transmitted abroad. Unlike others who’ve imported the virus from China or from people who have recently been to China, the woman in her 30s contracted the illness while in Iran.
“Any imported cases linked to Iran could be an indicator that there is more widespread transmission than we know about,” said Canada’s chief medical officer Dr. Theresa Tam Friday.
Canada has taken major steps to prevent the kind of shock that befell Ontario during the outbreak of the coronavirus known as SARS in 2003 that led to 44 deaths. Creating the Public Health Agency of Canada, which Tam heads, is one of them.
The country is now better co-ordinated, has increased its lab-testing capabilities and is prepared to trace people’s contacts to find people who might have caught a contagious illness without knowing it.
But once the number of incoming cases reaches a critical mass, the approach must change, according to infectious-diseases physician Dr. Isaac Bogoch of Toronto’s University Health Network.
He likens the response to trying to catch fly balls in the outfield: as the number of balls in the air increases, they become harder and harder to snag.
“Every health care system has limits,” Bogoch says. “The question is, if we start getting inundated with cases, how stretched can we get?”
Many emergency-room doctors argue Canada’s ERs are already as stretched as they can get and are worried about what would happen if they suddenly had to start treating COVID-19 cases en masse.
From the public-health perspective, the greatest challenge may be as simple communicating across all parts of the health system across the country, said Dr. Jasmine Pawa, president of the Public Health Physicians of Canada.
“We cover a very wide geographic area,” she said, though she added that Canada has made great strides over the course of the SARS experience and the H1N1 flu outbreak in 2009.
Dr. Alan Drummond of the Canadian Association of Emergency Physicians, who works at the hospital in Perth, Ont., says he doesn’t want to fearmonger, especially considering all the lessons Canada has learned from past outbreaks, but the reality of life in the ER gives him pause.
“Our day-to-day experience in crowded hospitals, unable to get the right patient in the right bed on a day-to-day basis … makes us really question what the integrity of our health-care system would be like in a major severe pandemic,” Drummond says.
He envisions that a disease like COVID-19, if it spread widely, would have a major impact, including the possibility of cancelled surgeries and moving stable patients out of hospitals who would otherwise stay.
“I think there would have to be hard decisions made about who lives and who dies, given our limited availability by both speciality and (intensive-care) beds and we would probably see some degree of health-care rationing,” he says.
The problem may be even more pronounced because of Canada’s aging population, he said. The virus tends to hit older people harder, according to observations made in China and abroad, and is also particularly dangerous for people with other health problems.
Older people also tend to stay admitted in hospital beds even when they are in relatively stable condition because of a lack of long-term-care beds across the country.
That keeps emergency rooms from being able to move acute patients out of the ER and into those beds, limiting hospitals’ capacity to handle new cases.
Tam agreed Friday that hospital capacity is a “critical aspect” of Canada’s preparedness for a potential coronavirus outbreak, but said even very bad flu seasons can have a similar effect on emergency rooms.
“If we can delay the impact of the coronavirus until a certain period, when there’s less influenza for example, that would also be very helpful,” she said.
She also suggested people who are concerned about the possibility that they’re developing COVID-19 symptoms should call ahead to a hospital so they can make proper arrangements for containment and isolation.
Canada is doing its best, along with every other country in the world, to seize this time of relative containment and plan ahead, Tam said.
Laura Osman, The Canadian Press
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