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Immune checkpoint inhibitors are waging a revolutionary war on cancer, but new research challenges the central dogma of how this drug treatment works. This research, published in the prestigious Journal of Clinical Investigation, shows for the first time that often-overlooked immune cells called Natural Killer (NK) cells that play a crucial role in responding to checkpoint inhibitors.
“Checkpoint inhibitors work by waking up the body’s own immune system and unleashing an immune attack on cancer cells,” explains co-senior author Dr. Michele Ardolino, a scientist at The Ottawa Hospital and assistant professor at the University of Ottawa. “For many years, everyone assumed that checkpoint inhibitors targeted immune cells called T-cells. But our research shows that they also target Natural Killer cells and these cells play a key role in the how this treatment works.”
Dr. Arolino led the study together with Dr. David Raulet, a professor at the University of California at Berkeley.
“In the cancer immunotherapy field there has been a singular focus on mobilizing antitumour T-cells, says Dr. Raulet. “We believe that NK cells have an important place at the table. Checkpoint therapy combined with other NK-directed immunotherapies may enable us to target many types of tumours that are currently non-responsive to available therapies.”
T-cells and NK cells can both recognize and kill cancer cells, but they do so in very different ways. NK cells recognize patterns of changes on cancer cells and are the immune system’s first line of defense. A T-cell, on the other hand, recognizes a single abnormal molecule on a cancer cell and initiates a more focused attack.
In the current study, Drs. Ardolino, Raulet and their colleagues investigated the effect of checkpoint inhibitors in various mouse models of cancer. They found that checkpoint inhibitors could shrink tumours even in mice with no anti-cancer T-cells, meaning that some other kind of cell must be responding to the checkpoint inhibitors. When the mice were depleted of NK cells, it greatly reduced or eliminated the anticancer effect of the checkpoint inhibitors. They also showed that NK cells produce the same checkpoint receptor molecules that T cells do, inferring they can respond directly to checkpoint inhibitors.
Previously, Dr. Ardolino, worked in Dr. Raulet’s lab in California before he was recruited to The Ottawa Hospital and the University of Ottawa in 2016. Together they are now investigating approaches to further enhance the cancer-killing ability of NK cells.
“My dream is that when people come to the hospital with cancer, we’ll be able to take a biopsy and determine not only the mutations in their cancer, but also profile how their immune system is interacting with their cancer,” says Dr. Ardolino. “Then we would give the patient the immunotherapy treatments that is most likely to work for them.”
To see this story online visit https://biotechnologyfocus.ca/ revolutionary-immunotherapy-researchreveals-wages-war-on-cancer/
international study creates urine test that detects tuberculosis in hiv patients
A new way to test for tuberculosis has come to town. Developed in part by University of Alberta researchers, this urine test can detect tuberculosis in people living with HIV earlier and more quickly than before.
Tuberculosis kills millions around the world every year and is the leading cause of death for people living with HIV. It is an infectious disease that mainly affects the lungs and is spread through droplets released into the air by coughs or sneezes. The new urine test will improve the speed and accuracy of diagnosis, providing earlier treatment and improving health outcomes.
“The test works by using an antibody to detect the presence of a carbohydrate produced by the organism that causes tuberculosis,” explains UofA chemist Todd Lowary, who is a collaborator on the project. “Pointof-care tests are important as they can be done in areas where the access to health care is low and comparatively unsophisticated.”
Lowary, an expert in carbohydrate synthesis and the Raymond Lemieux Professor of Carbohydrate Chemistry, was part of an international team, including the Foundation for Innovative New Diagnostics and Fujifilm, that developed the test, called Fujifilm SILVAMP TB LAM.
“Our contribution was to screen the specificity of a selection of possible antibodies against a panel of different carbohydrates to identify the best one antibody,” says Lowary. “That led to the increased sensitivity of the diagnostic.”
The group has issued a call for trial partners for those who wish to pilot the test in clinical settings. Studies to test the new test’s efficacy with HIV-negative patients and new antibodies are being developed to enhance the test’s performance.
The research was conducted with support from the Alberta Glycomics Centre and the Bill and Melinda Gates Foundation.
Todd Lowary (Photo Credit: John Ulan)
To see this story online visit https://biotechnologyfocus.ca/ international-study-creates-a-urine-testthat-detects-tuberculosis-in-hiv-patients/
Research suggests the gut microbiome may play a bigger role than you think Mcgill researchers unearth way to weaken drug-resistant bacteria
The word microbiome is becoming more common to hear and may play a bigger role than you think when it comes to your health. New research from scientists at the University of Alberta explore the idea of if the first bacteria introduced into the gut will have a lasting impact and may determine how susceptible one may be to ward off serious chronic diseases.
The findings by UofA microbial ecologist Jens Walter and his colleagues suggest differences in our microbial makeup likely depend on when we acquire our first microorganisms after birth—and the order they arrive in our gut.
The discovery presents an interesting topic of discussion on how these microbiomes—which are as personal as fingerprints—establish themselves and what drives their unique nature. That’s key to figuring out how to change our microbiomes for the better, says Walter.
“Each of us harbours a microbiome that is vastly distinct, even for identical twins. Microbiomes are important for our health, but they appear to be shaped by many unknown factors, so it’s hugely important to understand why we are all different,” he adds.
Studies have already shown that a person’s genetics, diet, environment, lifestyle and physiological state all make small contributions to the variation of the gut microbiome. But those factors account for less than 30 per cent of the variation.
In the study, researchers introduced distinct microbial communities, collected one at a time, from adult mice into the gastrointestinal tracts of young, genetically identical mice. The results showed that the microbiome in the adults was more like the microbiome introduced first. Even when using a cocktail of four distinct types of bacteria, the researchers repeatedly found that the first microbes showed the highest level of persistence and the strongest influence on how the gut microbiome developed.
The discovery about timing brings scientists one step closer to understanding how microbiomes might become disrupted— for example, through caesarean section birth or antibiotic use—which is then more likely to predispose us to chronic diseases, and how to potentially address that.
Poor gut health has been linked to obesity, Type 2 diabetes, heart disease, inflammatory bowel disease, colon cancer, neurological disorders, autism and allergies.
“If we know what drives specific microbiomes in specific people, we can have a much more rational approach to potentially altering the microbiome, and developing strategies to address those diseases,” says Walter. “Having long-term persistence of microbes when they colonize in the gut early in life means that a health-promoting biome could potentially be established by introducing beneficial bacteria straight after birth.”
There are such methods out there— such as some baby formulas spruced up with probiotics—but knowing more about how probiotics affect other members of the gut’s microbial community could bump it up another notch.
“We could be a lot more systematic,” states Walter. “I think in 30 or 40 years we’ll be able to colonize infants with specific bacteria we know are health-promoting and shape the microbiome in a beneficial way.”
To see this story online visit https://biotechnologyfocus.ca/research-suggests-the-gut-microbiomemay-play-a-bigger-role-than-you-think/ Antimicrobial resistance is a growing global issue that threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses, and fungi. To avert this from happening, researchers have been hard at work to unearth solutions – before it’s too late.
Scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) have discovered a new cellular target that can weaken the bacterium Pseudomonas aeruginosa, an intimidating microbe which can become highly tolerant to many antibiotics, and consequently refractory to antibiotic therapy. The team’s findings are published in Proceedings of the National Academy of Sciences (PNAS).
“We identified a new function important to antibiotic tolerance, which could be targeted to enhance the activity of our current antibiotics,” says lead study author Dr. Dao Nguyen, a scientist from the Translational Research in Respiratory Diseases Program at the RI-MUHC and an associate professor of Medicine at McGill University. “This is critical if we want to improve the efficacy of our antibiotics and prevent such treatments from failing.
The Centres for Disease Control and Prevention (CDC) in the United States has listed P. aeruginosa as one of the “nightmare bacteria”, with an impact of roughly 51,000 health care-associated infections each year that results in over 400 possibly preventable deaths. It is a common cause of pneumonia, surgical site infections, bloodstream or urinary tract infections.
The researchers thought that if they inhibit the enzyme activity or the stress signaling system, they could render the pathogen more susceptible to antibiotics; and as it turns out, they were right.
This research that Dr. Nguyen and her team have done may prove to be extremely valuable as the world progresses towards a more drug-resistant future. Without effective antibiotics, the world will be in peril, as treatments such an chemotherapy, invasive surgery, or even a small wound may be jeopardized. This threat requires immediate global action from all government sectors and society.
To see this story online visit https://biotechnologyfocus.ca/mcgillresearchers-unearth-way-to-weakendrug-resistant-bacteria/
