PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Disrupting a single gene could improve CAR T cell immunotherapy, new study shows

Disrupting a single gene could improve CAR T cell immunotherapy, new study shows
2023-11-14
(Press-News.org) CAR T cell therapy, a powerful type of immunotherapy, has begun to revolutionize cancer treatment. Pioneered at Memorial Sloan Kettering Cancer Center (MSK), the therapy involves engineering a patient’s T cells so they recognize and attack cancer cells. These CAR (chimeric antigen receptor) T cells are then multiplied in a lab and given back to the patient to be a continual fighting force against the cancer.

New research from the lab of physician-scientist Michel Sadelain, MD, PhD, shows that disrupting a single gene in the CAR T cells can make them more potent and able to fight tumors longer.

Impact of the SUV39H1 Gene on CAR T Cell Therapy In a paper published in Cancer Discovery, the team demonstrated that disrupting the gene SUV39H1 causes a ripple effect: It restores the expression of multiple genes that help sustain the T cells’ longevity. The researchers showed that this approach improved CAR T cell effectiveness against multiple cancers in mice.

“If we could help CAR T cells maintain their function by disrupting just one gene, it opens up a wide range of therapeutic benefits,” says Nayan Jain, PhD, a member of the Sadelain lab and the study’s co-first author.

Many patients have undergone several kinds of chemotherapy before receiving a CAR T treatment, he explains. As a result, their T cells are depleted and stressed, which makes it hard for them to multiply and effectively fight the cancer.

“This new approach requires fewer CAR T cells and therefore could expand the pool of patients that could be eligible for this treatment,” Dr. Jain says. “It could also increase the effectiveness of the CAR T therapy for each patient.”

“With this new approach, CAR T cells augment their longevity and maintain their tumor-killing function simultaneously, so we can use a lower dose to treat the patients, which may reduce a severe side effect called cytokine release syndrome (CRS),” says co-first author Zeguo Zhao, PhD, also of the Sadelain lab.

Overcoming T Cell Exhaustion in CAR T Cell Therapy The tendency of CAR T cells to lose their function over time — a phenomenon known as T cell exhaustion — has been a major treatment hurdle. Even when the CAR T cells are effective in the short term, the cancer often comes back. This problem explains in part why CAR T cell therapy has not worked as well against solid tumors (which account for most cancers) as it has for blood cancers.

Dr. Sadelain, Director of the Center for Cell Engineering, first engineered T cells 30 years ago and has been continuously striving to improve CAR T cells. Earlier research by the Sadelain team revealed that T cell exhaustion can happen when certain genes in the T cells are turned off. And what turns off these genes? The answer lies in the epigenetics of cells.

Think of epigenetics like a dimmer switch on DNA — lowering the lights without changing the lamp fixture. Likewise, epigenetics can alter gene expression without changing the DNA sequence.

How Changing One Gene Could Impact Many Many epigenetic changes occur because of the way DNA is packaged in the nucleus of a cell. The DNA strands are wrapped around spool-like proteins called histones. In regions where the DNA and proteins are packed tightly, the genes are inaccessible and cannot be turned on.

The researchers noticed that the epigenetic changes disabling a number of helpful genes were in part regulated by SUV39H1. This single gene caused the other genes to be shut down.

“We decided that rather than trying to change the expression of all those different genes individually, we could just focus on disrupting SUV39H1,” Dr. Jain says. “This would allow us to fine-tune the expression of multiple genes at once to enhance T cell function.”

Study Results Using CRISPR/Cas9 Technology To Edit the SUV39H1 Gene The researchers used the gene-editing tool CRISPR/Cas9 to alter SUV39H1 in human CAR T cells. They placed these modified CAR T cells into mice that had been implanted with either human leukemia cells or prostate cancer cells. For both cancers, the CAR T cells were able to sustain their function without becoming exhausted, leading to tumor elimination. By contrast, mice with unedited CAR T cells did not survive the cancer.

“The edited CAR T cells can maintain their anti-cancer effects, even when we challenged them repeatedly by exposing them to new tumors over time,” Dr. Zhao says. “These results suggest that SUV39H1-edited CAR T cells may reduce tumor relapse in patients.”

There did not appear to be serious side effects in the mice, although researchers will need to confirm the safety of this approach in humans. The biotechnology company Mnemo Therapeutics is exploring the possibility of conducting clinical trials based on this research.

Dr. Jain credits the expertise and resources of the Core Facilities at the Sloan Kettering Institute — a hub for basic and translational research within MSK — to make this discovery possible, as well as MSK’s Center for Epigenetics Research and the Integrated Genomics Operation.

“There are many really advanced technologies needed for these kinds of studies that we can’t do ourselves in the lab,” Dr. Jain says. “Having other experts available in-house vastly accelerated our work.”

This research was supported by Mnemo Therapeutics, the Pasteur Weizmann/Servier Prize and the Fondation ARC Léopold Griffuel Award (both awarded to Dr. Sadelain), and MSK Core Grant P30 CA008748.

Dr. Sadelain and MSK are shareholders in Mnemo Therapeutics, which holds license to patents on SUV39H1 inactivation.

END

[Attachments] See images for this press release:
Disrupting a single gene could improve CAR T cell immunotherapy, new study shows

ELSE PRESS RELEASES FROM THIS DATE:

UIUC professors receive AFOSR grant to study detrimental defects in superconducting qubit junctions

UIUC professors receive AFOSR grant to study detrimental defects in superconducting qubit junctions
2023-11-14
University of Illinois Urbana-Champaign professors Angela Kou (Physics), Pinshane Huang (MatSE), Wolfgang Pfaff (Physics) and Andre Schleife (MatSE) have received an Air Force Office of Scientific Research grant for their project “Identifying the origin and lossy defects in Josephson junctions”. The two-year, nearly $1 million grant aims to take a materials science approach to address the detrimental defects of Josephson junctions in superconducting qubits. The current state of quantum computing is called the noisy intermediate-scale quantum ...

Mirvie announces completion of enrollment of 10,000 person landmark research study for pregnancy health

2023-11-14
South San Francisco, CA (November 14, 2023) – Mirvie, a company pioneering the prediction of life-threatening pregnancy complications months in advance, today announced the completion of enrollment of its landmark 10,000 person research study for pregnancy health, in collaboration with leading experts in obstetrics and maternal-fetal medicine. “This monumental effort represents a new chapter for pregnancy health,” said Maneesh Jain, CEO and co-founder of Mirvie. “Today, we face a massive crisis in maternal health, and innovative solutions are desperately needed. The audacious scale of this generalizable study – involving over 10,000 individuals – ...

Study finds strongest evidence yet for local sources of cosmic ray electrons

Study finds strongest evidence yet for local sources of cosmic ray electrons
2023-11-14
A new study using data from the CALorimetric Electron Telescope (CALET) instrument on the International Space Station has found evidence for nearby, young sources of cosmic ray electrons, contributing to a greater understanding of how the galaxy functions as a whole.  The study included more than seven million data points representing particles arriving at CALET’s detector since 2015, and CALET’s ability to detect electrons at the highest energies is unique. As a result, the data includes more electrons at high energies than any previous work. That makes the statistical analysis of the data more robust and lends support to the conclusion that there are one or more local ...

Special Issue of Criminology & Public Policy examines cybercrime and cybersecurity

2023-11-14
Cybercrime—computer hacking, social engineering, intellectual property theft, electronic fraud, online interpersonal violence, identity theft, and Internet-facilitated sexual victimization—is a leading threat to national security, with millions of victims in both the United States and around the world, and billions of dollars being spent to combat it. Criminology and related disciplines are just beginning to understand cybercrime and how best to deter and prevent it—or at least reduce its harms. ...

Special issue of Medicare Care supports the need to study economic impacts on patient outcomes

2023-11-14
November 14, 2023 — A special supplemental issue of Medical Care, sponsored by the Assistant Secretary for Planning and Evaluation (ASPE) in the U.S. Department of Health and Human Services, supports the growing recognition that economic factors often affect health outcomes, patient decision-making, and equity in health care. Medical Care, the official journal of the Medical Care Section of the American Public Health Association, is published in the Lippincott portfolio by Wolters Kluwer.  The scope of patient-centered outcomes research (PCOR) was expanded to include economic outcomes in the 2019 reauthorization ...

Alcohol consumption and epigenetic age acceleration across human adulthood

Alcohol consumption and epigenetic age acceleration across human adulthood
2023-11-14
“Our findings may help to understand the role of alcohol-associated biological aging in the development of age-related diseases such as CVD and cancer.” BUFFALO, NY- November 14, 2023 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 20, entitled, “Alcohol consumption and epigenetic age acceleration across human adulthood.” The alcohol-associated biological aging remains to be studied across adulthood. In their new study, ...

How one lab at MSK is working to harness the power of the immune system against cancer

How one lab at MSK is working to harness the power of the immune system against cancer
2023-11-14
Investigator Ming Li, PhD, has dedicated his career to understanding the intricate workings of the immune system — both in general and for the critical role it plays in cancer. Study by study, his lab at Memorial Sloan Kettering Cancer Center (MSK) is sharing new insights into the molecular and cellular mechanisms involved in immune regulation — a type of knowledge-building that scientists call “basic science” or “discovery science.” But Dr. Li is equally focused ...

University of Kentucky researcher helps solve 60-year mystery inside heart, publishes in Nature

University of Kentucky researcher helps solve 60-year mystery inside heart, publishes in Nature
2023-11-14
LEXINGTON, Ky. (Nov. 14, 2023) — One University of Kentucky researcher has helped solve a 60-year-old mystery about one of the body’s most vital organs: The heart. Kenneth S. Campbell, Ph.D., the director of translational research in the Division of Cardiovascular Medicine in the UK College of Medicine, helped map out an important part of the heart on a molecular level. The study titled “Cryo-EM structure of the human cardiac myosin filament” was published online in the prestigious journal Nature earlier this month. The heart is made up of billions of cells. Each cell contains thousands ...

Melting ice falling snow: Sea ice declines enhance snowfall over West Antarctica

2023-11-14
UNIVERSITY PARK, Pa. — As the world continues to warm, Antarctica is losing ice at an increasing pace, but the loss of sea ice may lead to more snowfall over the ice sheets, partially offsetting contributions to sea level rise, according to Penn State scientists. The researchers analyzed the impacts of decreased sea ice in the Amundsen Sea in West Antarctica and found the ice-free ocean surface leads to more moisture in the atmosphere and heavier snowfalls on the ice sheet, the team reported in the journal Geophysical Research Letters. While the additional snowfall is not enough to offset the impacts of melting ice, including it in climate ...

Dangerous bee virus less deadly in at least one US forest, researchers find

2023-11-14
UNIVERSITY PARK, Pa. — This year’s cold and flu season is bringing good news for honey bees: Penn State researchers have found that the deadly deformed wing virus (DMV) may have evolved to be less deadly in at least one U.S. forest. The findings could have implications for preventing or treating the virus in managed colonies, researchers said. The study, which was recently published in the Proceedings of the Royal Society B, compared rates and severity of DWV in wild honey bees from ...

LAST 30 PRESS RELEASES:

Predictable structures in music synchronises blood pressure the most, and could be used to create personalized music-based cardiovascular therapies  

New systematic review and meta-analysis shows an association between shingles vaccination and lower risk of heart attack and stroke 

Food for thought: Using food delivery services to provide rapid cardiac arrest response and potentially save lives

College drinking linked to poor academics, mental health for those around the drinker: Study

Nearly 80% of whale sharks in this marine tourism hotspot have human-caused scars

Spider uses trapped fireflies as glowing bait to attract more prey

How AI can build bridges between nations, if diplomats use it wisely

80% of Americans don’t know early-stage prostate cancer often has no symptoms

Researchers engineer ureter tissue from stem cells, paving way for transplantable kidneys

Strong, evidence-based leadership at CDC essential in wake of director’s exit, says SHEA

Birdwatching tourism is booming. Some countries are benefiting, while others are left behind

High protein or Trp diet increases the risk of cancer-associated venous thromboembolism

Risk of a second cancer after early breast cancer is low

Genetic key to why immune responses differ between men and women

Discovery could lead to new treatments for life-threatening allergic reactions

CRF announces TCT 2025 late-breaking clinical trials and science

Ancient DNA reveals farming spread through migration, locals slow to adopt it

Researchers turn mouse scalp transparent to image brain development

New research reveals longevity gains slowing, life expectancy of 100 unlikely

Wheat that makes its own fertilizer

Certain communities of pond plants may increase greenhouse gases

Hormone therapy type matters for memory performance after menopause

Stroke risk highest among Native Hawaiian, Pacific Islander people

Scientists reveal warped protoplanetary discs, reshaping ideas about how planets form

Be it feast or famine, orangutans adapt with flexible diets

Insomnia patients report better sleep when taking cannabis-based medical products

Intrusive distracting thoughts may be associated with anxiety and linked to lower well-being, and occur more often when alone than in company

New crocodile-relative “hypercarnivore” from prehistoric Patagonia was 11.5ft long and weighed 250kg

“Unhappiness hump” in aging may have disappeared worldwide

Breathwork can induce altered states of consciousness linked with changes in brain blood flow

[Press-News.org] Disrupting a single gene could improve CAR T cell immunotherapy, new study shows