(Press-News.org) Using laboratory-grown cells from humans and genetically engineered mice, scientists at Johns Hopkins Medicine say they have evidence that modifying a specific protein in immune white blood cells known as CD8+ T cells can make the cells more robust, potentially opening the door for better use of people’s own immune system T cells to fight cancer.
The findings were published Oct. 3 in the journal JCI-Insight.
“Maximizing the effectiveness of T-cell-based therapies remains a critical challenge,” says David Kass, M.D., Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine and senior author of the study. “We’ve identified a powerful way to boost T cell function, offering a promising avenue for improving cancer immunotherapy and potentially treating a wide range of infectious and other diseases.”
Kass and his team emphasize that their experiments to date are preclinical, and will require significant further laboratory-based efforts before they can be applied to human therapies.
For the current study, Kass and his team focused on CD8+ T cells, the circulating immune system “soldiers” responsible for identifying and fighting infections and cancer cells.
A protein called TSC2 (tuberous sclerosis protein 2) can activate or block a molecular pathway that regulates the T cells.
Overall, their experiments show that introducing a mutation in the TSC2 gene acts as a molecular “volume knob” to dial up or down the T cells’ regulatory pathway when it’s actively responding to immune challenges such as a virus or a cancer antigen. Like a volume knob, there is no change until the music starts — then it is louder. The researchers found the mutated T cells were acting no differently than normal ones when they were just resting and not being stimulated to attack a target. They only became more active when stimulated. This type of control is relatively new for T cells.
This discovery, Kass says, raises the possibility of enhancing a therapy known as CAR-T, in which T cells are genetically engineered to better recognize a particular cancer. If these T cells also had the mutation in the TSC2 gene, the T cells could be more active against the tumor by multiplying, but could also persist longer, enhancing the T cells’ effectiveness to kill cancer.
The scientists also found that the T cells containing the TSC2 mutation could expand in great numbers during the initial immune response, but then could also persist long-term, which differs greatly from other T cells used for therapy.
The T cells with the TSC2 mutation were also better able to multiply and be activated to fight infections and to counter tumors, despite being in an environment that was more acidic or had lower oxygen than their nonmutated counterparts.
“After testing our modified T cells, we found they were better at stopping tumor growth, proliferated more inside the tumor and didn’t get tired out as easily,” Kass says. “As we continue to unravel the complexities of the immune system, such innovative approaches hold promise for revolutionizing the field of immunotherapy.”
In recent years, dozens of immunotherapies with novel drugs and antibodies have come on the market to treat cancer and other diseases, but response rates in patients vary widely, and overall, their optimal effectiveness as a group is only in the 15%–20% range. There is room for improvement, and many ongoing efforts are underway to do this. The new results may ultimately contribute to those efforts.
The researchers plan to do further studies with solid tumors such as lung, liver and colon cancers, which, compared with blood tumors such as leukemia, have been harder to achieve complete success with T cell-based therapies.
Additional authors of the study include Chirag Patel, the primary researcher for the work, and Jonathan Powell, both formerly with the Bloomberg~Kimmel Institute for Immunotherapy and now with Calico Life Sciences LLC; Yi Dong, Xiaoxu Wang and Jiayu Wen with the Bloomberg~Kimmel Institute for Immunotherapy; Navid Koleini, Brittany Dunkerly-Eyring and Mark Ranek with the Johns Hopkins University School of Medicine Division of Cardiology; and Laura Bartle, Daniel Henderson and Jason Sagert with CRISPR Therapeutics.
Patel, Dunkerly-Eyring, Ranek, Kass and Powell have filed a patent for the use of TSC2 mutations at Serine 1364 and Serine 1365 (human) to treat disease.
This study was supported by the National Institutes of Health and the Bloomberg Kimmel Institute for Cancer Immunotherapy.
END
Researchers report protein mutation creates ‘super’ T cells with potential to fight off cancer and infections
T cells that carry specific mutation have potential to improve cancer immunotherapy
2023-10-03
ELSE PRESS RELEASES FROM THIS DATE:
Enhancing the efficiency of plant regeneration
2023-10-03
Crop modification can be traced to the beginning of agriculture and human civilization.
Native Americans, for example, developed corn from a wild grass called teosinte more than 7,000 years ago.
Methods to increase crop resiliency and sustainability have evolved, and improved, over time. Biotechnology, or the use of biology to develop new products and organisms, is an application that holds great promise for impactful changes to the agricultural systems. Through this method, the DNA in plant cells is modified — for instance ...
Registration now open for Energy Department’s National Science Bowl®
2023-10-03
Washington, D.C. – Registration is open for the 34th National Science Bowl® (NSB), hosted by the U.S. Department of Energy (DOE) Office of Science. Thousands of students compete in the contest annually as it has grown into one of the largest academic math and science competitions in the country.
Teams – four or five students and a teacher who serves as a coach – can sign up to participate in the NSB by registering with the coordinator for their regional competition. Details can be found on the NSB registration page. The competition is divided into two categories: high school and middle school. Regional competitions typically last one or two days ...
Disaster-proofing sustainable neighborhoods requires thorough long-term planning, new Concordia study shows
2023-10-03
Individual neighbourhoods will be intimately involved in providing local solutions to collective problems. One measure will be distributed renewable energy production — energy produced at local levels, either by solar technology, wind or other methods, will push cities to achieve their net-zero targets.
However, even these power-generating neighbourhoods will remain vulnerable to power outages resulting from natural disasters such as hurricanes, fires or floods. And all of these are likely to become increasingly common due to the effects of climate change. ...
Carbon-capture tree plantations threaten tropical biodiversity for little gain, ecologists say
2023-10-03
The increasingly urgent climate crisis has led to a boom in commercial tree plantations in an attempt to offset excess carbon emissions. However, authors of a peer-reviewed opinion paper publishing October 3 in the journal Trends in Ecology and Evolution argue that these carbon-offset plantations might come with costs for biodiversity and other ecosystem functions. Instead, the authors say we should prioritize conserving and restoring intact ecosystems.
“Despite the broad range of ecosystem functions and services provided ...
Can science take the STING out of runaway inflammation?
2023-10-03
CINCINNATI—Until the COVID-19 pandemic exploded, few people outside of research labs and intensive care units had heard of a cytokine storm. But once this dangerous form of infection-triggered runaway inflammation started claiming lives by the thousands, a legion of scientists jumped into the hunt for ways to calm these storms.
Now, a study led by immunobiology experts at Cincinnati Children’s, offers important new details on how two elements of our body’s immune system clash with each other to prompt a chain of reactions that can release deadly floods of cell-killing, organ-damaging ...
Adherence to CPAP treatment and the risk of recurrent cardiovascular events
2023-10-03
About The Study: The results of this meta-analysis indicate that adherence to continuous positive airway pressure (CPAP) was associated with a reduced major adverse cardiac and cerebrovascular event recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with obstructive sleep apnea.
Authors: Ferran Barbé, M.D., of the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) in Madrid, is the corresponding author.
To access the ...
Spending on mental health services for kids and adolescents has risen by more than 25% since beginning of pandemic
2023-10-03
Spending on mental health services for children and adolescents has risen by more than one-quarter since the beginning of the COVID-19 pandemic, continuing to rise even as the use of telehealth plateaued, according to a new RAND Corporation study.
Spending on mental health for people aged 19 and younger rose by 26% from March 2020 to August 2022 among a large group whose families have employer-provided insurance. During the same period, use of mental health services increased by 22%.
The study found that use of telehealth for pediatric patients increased more than 30-fold during the early months of the pandemic and remained ...
Surgical scorecards may cut cost of surgical procedures without impacting outcomes
2023-10-03
Key takeaways
A tool for evaluating the overall cost of a surgical procedure, called a scorecard, helps reduce costs of surgical procedures between 5% and 20% without adversely affecting clinical outcomes.
Further implementation of scorecards may move surgeons toward energy-efficient operating rooms, which are the largest hospital producer of emissions and waste.
CHICAGO (October 3, 2023): Surgical scorecards, a tool that gives direct feedback ...
Utilization and spending on mental health services among children and youths with commercial insurance
2023-10-03
About The Study: After comparing mental health care service utilization and spending rates for children and youths with commercial insurance across three periods from January 2019 through August 2022, this study found differences between periods as well as different rates of change within each period for both visit types (in-person and telehealth), even after accounting for state and patient sex. Utilization and spending increased over the entire timeframe. Attention-deficit/hyperactivity disorder, anxiety disorders, and adjustment disorder accounted for most visits and spending in all phases.
Authors: Mariah ...
Psychotropic medication use in children and adolescents with type 1 diabetes
2023-10-03
About The Study: This study found an increasing trend in psychotropic medication dispensation among Swedish children and adolescents with type 1 diabetes from 2006 to 2019, persistently higher than those without type 1 diabetes. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.
Authors: Shengxin ...
LAST 30 PRESS RELEASES:
Thirty-year mystery of dissonance in the “ringing” of black holes explained
Less intensive works best for agricultural soil
Arctic rivers project receives “national champion” designation from frontiers foundation
Computational biology paves the way for new ALS tests
Study offers new hope for babies born with opioid withdrawal syndrome
UT, Volkswagen Group of America celebrate research partnership
New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll
Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes
University of Cincinnati Cancer Center presents research at AACR 2025
Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025
AACR: Researchers share promising results from MD Anderson clinical trials
New research explains why our waistlines expand in middle age
Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker
Chips off the old block
Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia
Cutting the complexity from digital carpentry
Lung immune cell type “quietly” controls inflammation in COVID-19
Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity
State and sociodemographic trends in US cigarette smoking with future projections
Young adults drive historic decline in smoking
NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research
Chimpanzee stem cells offer new insights into early embryonic development
This injected protein-like polymer helps tissues heal after a heart attack
FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology
In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity
Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects
A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions
AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate
Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative
Structure dictates effectiveness, safety in nanomedicine
[Press-News.org] Researchers report protein mutation creates ‘super’ T cells with potential to fight off cancer and infectionsT cells that carry specific mutation have potential to improve cancer immunotherapy