New technology using CRISPR to enhance the immune system’s ability to detect cancer cells has been created, potentially paving the way for innovative cancer treatment methods.
Major histocompatibility complex (MHC) class I molecules are an immune complex present on the surface of all cells in humans. MHC class I molecules are a prerequisite for the immune system to recognize and eliminate cancer. When cancer cells are faced with pressure from the immune system, they actively reduce their MHC class I molecules, so cancer cells can hide from drawing the attention of CD8+ T cells, the immune system’s primary cancer-fighting cells.
Researchers in Japan and the United States, led by Professor Koichi Kobayashi of Hokkaido University and Texas A&M Health Center, and Dr. Paul de Figueiredo, Bond LSC principal investigator and NEXTGEN Precision Health endowed professor at the University of Missouri, have developed technology to robustly augment the amount of MHC class I in cancer cells. This development, a novel method for boosting the immune system’s capability to detect and eliminate cancer cells, was published in the journal Proceedings of the National Academy of Sciences.
Revolutionary Technology for Cancer Immunotherapy
“Our discovery has the potential to transform the way we approach cancer treatment,” says Kobayashi. “Our technology enables us to specifically target immune responsive genes and activate the immune system against cancer cells, offering hope to those who are resistant to current immunotherapy.”
Compared with untreated cancer, the TRED-I system significantly reduced cancer size in mice models. Credit: Xin Sun, et al. Proceedings of the National Academy of Sciences. January 29, 2024
Kobayashi and his team previously identified a gene, called NLRC5, that regulates MHC class I levels. They further found that NLRC5 is suppressed by turning off molecular switches existing on DNA in cancers—through a process called DNA methylation—to reduce levels of MHC class I.
Promising Results and Future Directions
Their technology, known as TRED-I (Targeted Reactivation and Demethylation for MHC-I) system, was able to restore DNA methylation of NLRC5 gene and further activate NLRC5, thus increasing MHC class I levels in cancer without causing severe side effects.
“New modalities for fighting cancer like this are desperately needed because we have few solutions to fight some cancer types,” said de Figueiredo. “This is a radically new approach, and I’ve felt lucky to be part of it.”
TRED-I was tested with animal cancer models. It reduced tumor sizes significantly and increased the activity of cytotoxic CD8+ T cells. When used in conjunction with existing immunotherapy, TRED-I markedly enhanced treatment efficacy.
Unexpectedly, the TRED-I system was effective for the tumor distantly located from the original targeted tumor, showing potential to treat metastasized cancers.
“This work is the culmination of our team’s research over the past decade,” Kobayashi concludes. “It’s great to shed light on moving our findings to potential clinical applications. We believe with further refinement, the TRED-I system could contribute significantly to cancer therapy.”
Further research will focus on enabling direct delivery of the TRED-I system in cancer patients. Such drugs could improve the efficacy of the immune system in eliminating cancer and would be also able to improve the response to existing therapy.
Reference: “Targeted demethylation and activation of NLRC5 augment cancer immunogenicity through MHC class I” by Xin Sun, Toshiyuki Watanabe, Yoshitaka Oda, Weidong Shen, Alaa Ahmad, Ryota Ouda, Paul de Figueiredo, Hidemitsu Kitamura, Shinya Tanaka and Koichi S. Kobayashi, 1 February 2024, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2310821121
The study was funded by the Japan Society for the Promotion of Science, the Japan Agency for Medical Research and Development, the Japan Science and Technology Agency, the Takeda Science Foundation, Bristol-Myers Squibb, the SENSHIN Medical Research Foundation, the Hitachi Global Foundation, the Kobayashi Foundation for Cancer Research, and the Toyo Suisan Foundation.
News
This Startup Says It Can Clean Your Blood of Microplastics
This is a non-exhaustive list of places microplastics have been found: Mount Everest, the Mariana Trench, Antarctic snow, clouds, plankton, turtles, whales, cattle, birds, tap water, beer, salt, human placentas, semen, breast milk, feces, testicles, [...]
New Blood Test Detects Alzheimer’s and Tracks Its Progression With 92% Accuracy
The new test could help identify which patients are most likely to benefit from new Alzheimer’s drugs. A newly developed blood test for Alzheimer’s disease not only helps confirm the presence of the condition but also [...]
The CDC buried a measles forecast that stressed the need for vaccinations
This story was originally published on ProPublica, a nonprofit newsroom that investigates abuses of power. Sign up to receive our biggest stories as soon as they’re published. ProPublica — Leaders at the Centers for Disease Control and Prevention [...]
Light-Driven Plasmonic Microrobots for Nanoparticle Manipulation
A recent study published in Nature Communications presents a new microrobotic platform designed to improve the precision and versatility of nanoparticle manipulation using light. Led by Jin Qin and colleagues, the research addresses limitations in traditional [...]
Cancer’s “Master Switch” Blocked for Good in Landmark Study
Researchers discovered peptides that permanently block a key cancer protein once thought untreatable, using a new screening method to test their effectiveness inside cells. For the first time, scientists have identified promising drug candidates [...]
AI self-cloning claims: A new frontier or a looming threat?
Chinese scientists claim that some AI models can replicate themselves and protect against shutdown. Has artificial intelligence crossed the so-called red line? Chinese researchers have published two reports on arXiv claiming that some artificial [...]
New Drug Turns Human Blood Into Mosquito-Killing Weapon
Nitisinone, a drug for rare diseases, kills mosquitoes when present in human blood and may become a new tool to fight malaria, offering longer-lasting, environmentally safer effects than ivermectin. Controlling mosquito populations is a [...]
DNA Microscopy Creates 3D Maps of Life From the Inside Out
What if you could take a picture of every gene inside a living organism—not with light, but with DNA itself? Scientists at the University of Chicago have pioneered a revolutionary imaging technique called volumetric DNA microscopy. It builds [...]
Scientists Just Captured the Stunning Process That Shapes Chromosomes
Scientists at EMBL have captured how human chromosomes fold into their signature rod shape during cell division, using a groundbreaking method called LoopTrace. By observing overlapping DNA loops forming in high resolution, they revealed that large [...]
Bird Flu Virus Is Mutating Fast – Scientists Say Our Vaccines May Not Be Enough
H5N1 influenza is evolving rapidly, weakening the effectiveness of existing antibodies and increasing its potential threat to humans. Scientists at UNC Charlotte and MIT used high-performance computational modeling to analyze thousands of viral protein-antibody interactions, revealing [...]
Revolutionary Cancer Vaccine Targets All Solid Tumors
The method triggers immune responses that inhibit melanoma, triple-negative breast cancer, lung carcinoma, and ovarian cancer. Cancer treatment vaccines have been in development since 2010, when the first was approved for prostate cancer, followed [...]
Scientists Uncover Hidden Protein Driving Autoimmune Attacks
Scientists have uncovered a critical piece of the puzzle in autoimmune diseases: a protein that helps release immune response molecules. By studying an ultra-rare condition, researchers identified ArfGAP2 as a key player in immune [...]
Mediterranean neutrino observatory sets new limits on quantum gravity
Quantum gravity is the missing link between general relativity and quantum mechanics, the yet-to-be-discovered key to a unified theory capable of explaining both the infinitely large and the infinitely small. The solution to this [...]
Challenging Previous Beliefs: Japanese Scientists Discover Hidden Protector of Heart
A Japanese research team found that the oxidized form of glutathione (GSSG) may protect heart tissue by modifying a key protein, potentially offering a novel therapeutic approach for ischemic heart failure. A new study [...]
Millions May Have Long COVID – So Why Can’t They Get Diagnosed?
Millions of people in England may be living with Long Covid without even realizing it. A large-scale analysis found that nearly 10% suspect they might have the condition but remain uncertain, often due to [...]
Researchers Reveal What Happens to Your Brain When You Don’t Get Enough Sleep
What if poor sleep was doing more than just making you tired? Researchers have discovered that disrupted sleep in older adults interferes with the brain’s ability to clean out waste, leading to memory problems [...]
