March 10, 2023
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Nearly two dozen experimental therapies targeting the immune system are in clinical trials for Alzheimer’s disease, a reflection of the growing recognition that immune processes play a key role in driving the brain damage that leads to confusion, memory loss and other debilitating symptoms.
Many of the immunity-focused Alzheimer’s drugs under development are aimed at microglia, the brain’s resident immune cells, which can injure brain tissue if they’re activated at the wrong time or in the wrong way. A new study from researchers at Washington University School of Medicine in St. Louis indicates that microglia partner with another type of immune cell — T cells — to cause neurodegeneration. Studying mice with Alzheimer’s-like damage in their brains due to the protein tau, the researchers discovered that microglia attract powerful cell-killing T cells into the brain, and that most of the neurodegeneration could be avoided by blocking the T cells’ entry or activation. The findings, published March 8 in the journal Nature, suggest that targeting T cells is an alternative route to preventing neurodegeneration and treating Alzheimer’s disease and related diseases involving tau, collectively known as tauopathies.
“This could really change the way we think about developing treatments for Alzheimer’s disease and related conditions,” said senior author David M. Holtzman, MD, Professor of Neurology. “Before this study, we knew that T cells were increased in the brains of people with Alzheimer’s disease and other tauopathies, but we didn’t know for sure that they caused neurodegeneration. These findings open up exciting new therapeutic approaches. Some widely used drugs target T cells. Fingolomid, for example, is commonly used to treat multiple sclerosis, which is an autoimmune disease of the brain and spinal cord. It’s likely that some drugs that act on T cells could be moved into clinical trials for Alzheimer’s disease and other tauopathies if these drugs are protective in animal models.”
Source: https://medicine.wustl.edu
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Tags: Alzheimer's, confusion, immune cells, immune system, memory loss, microglia, neurodegeneration, protein Tau, tauopathies, Washington University School of Medicine in St. Louis
March 7, 2023
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Some cities fight gangs with ex-members who educate kids and starve gangs of new recruits. Stanford Medicine researchers have done something similar with cancer — altering cancer cells so that they teach the body’s immune system to fight the very cancer the cells came from.
“This approach could open up an entirely new therapeutic approach to treating cancer,” said Ravi Majeti, MD, PhD, a professor of hematology and the study’s senior author. The research was published March 1 in Cancer Discovery. The lead author is Miles Linde, PhD, a former PhD student in immunology who is now at the Fred Hutchinson Cancer Institute in Seattle.
Some of the most promising cancer treatments use the patient’s own immune system to attack the cancer, often by taking the brakes off immune responses to cancer or by teaching the immune system to recognize and attack the cancer more vigorously. T cells, part of the immune system that learns to identify and attack new pathogens such as viruses, can be trained to recognize specific cancer antigens, which are proteins that generate an immune response. For instance, in CAR T-cell therapy, T cells are taken from a patient, programmed to recognize a specific cancer antigen, then returned to the patient. But there are many cancer antigens, and physicians sometimes need to guess which ones will be most potent.
A better approach would be to train T cells to recognize cancer via processes that more closely mimic the way things naturally occur in the body — like the way a vaccine teaches the immune system to recognize pathogens. T cells learn to recognize pathogens because special antigen presenting cells (APCs) gather pieces of the pathogen and show them to the T cells in a way that tells the T cells, “Here is what the pathogen looks like — go get it.” Something similar in cancer would be for APCs to gather up the many antigens that characterize a cancer cell. That way, instead of T cells being programmed to attack one or a few antigens, they are trained to recognize many cancer antigens and are more likely to wage a multipronged attack on the cancer. Now that researchers have become adept at transforming one kind of cell into another, Majeti and his colleagues had a hunch that if they turned cancer cells into a type of APC called macrophages, they would be naturally adept at teaching T cells what to attack.
“We hypothesized that maybe cancer cells reprogrammed into macrophage cells could stimulate T cells because those APCs carry all the antigens of the cancer cells they came from,” said Majeti, who is also the RZ Cao Professor, assistant director of the Institute for Stem Cell Biology and Regenerative Medicine and director of the Ludwig Center for Cancer Stem Cell Research and Medicine.
The study builds on prior research from the Majeti lab showing that cells taken from patients with a type of acute leukemia could be converted into non-leukemic macrophages with many of the properties of APCs. In the current study, the researchers programmed mouse leukemia cells so that some of them could be induced to transform themselves into APCs. When they tested their cancer vaccine strategy on the mouse immune system, the mice successfully cleared the cancer. “When we first saw the data showing clearance of the leukemia in the mice with working immune systems, we were blown away,” Majeti said. “We couldn’t believe it worked as well as it did.”
Source: https://med.stanford.edu/
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| Tags: antigens, APCs, cancer cells, CAR T-cell therapy, Fred Hutchinson Cancer Institute, immune system, Institute for Stem Cell Biology and Regenerative Medicine, leukemia, Ludwig Center for Cancer Stem Cell Research and Medicine, macrophages, proteins, Stanford Medicine, T-cells, virus
February 22, 2023
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Messenger RNA (mRNA) vaccines may be the hottest thing in science now, as they helped turn the tide against COVID-19. But even before the pandemic began, Memorial Sloan Kettering Cancer Center researchers had already been working to use mRNA vaccine technology to treat cancer. Vinod Balachandran a physician-scientist affiliated with the David M. Rubenstein Center for Pancreatic Cancer Research and the Parker Institute for Cancer Immunotherapy, is leading the only clinical trial to test mRNA vaccines for pancreatic cancer. The key to these vaccines appears to be proteins in the pancreatic tumors, called neoantigens, which alert the immune system to keep the cancer at bay.
The vaccines are custom-made for every person. The hope is that the vaccine will stimulate the production of certain immune cells, called T cells, that recognize pancreatic cancer cells. This could reduce the risk of the cancer returning after the main tumor was removed by surgery. In 8 of 16 patients studied, the vaccines activated T cells that recognize the patient’s own pancreatic cancers. These patients also showed delayed recurrence of their pancreatic cancers, suggesting the T cells activated by the vaccines may be having the desired effect to keep pancreatic cancers in check.
There has been great interest in using immunotherapy for pancreatic cancer because nothing else has worked very well. We thought immunotherapy held promise because of research we began about seven years ago. A small subset of patients with pancreatic cancer manage to beat the odds and survive after their tumor is removed. We looked at the tumors taken from these select patients and saw that the tumors had an especially large number of immune cells in them, especially T cells. Something in the tumor cells seemed to be sending out a signal that alerted the T cells and drew them in.
Source: https://www.thebrighterside.news/
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| Tags: cancer, cells, COVID-19, David M. Rubenstein Center for Pancreatic Cancer Research, immune cells, immune system, immunotherapy, Memorial Sloan Kettering Cancer Center, messenger RNA, mRNA, neoantigens, pancreatic cancer, pancreatic tumors, Parker Institute for Cancer Immunotherapy, proteins, T-cells, vaccines
February 10, 2023
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Cancer cells have a series of features that allow the immune system to identify and attack them. However, these same cells create an environment that blocks immune cells and protects the tumour. This means that immune cells cannot reach the cancer cells to remove them. The scientific community has been working for years to increase the effectiveness of the immune system against cancer by using vaccines based on dead tumour cells.
Scientists at IRB Barcelona, led by ICREA researcher Dr. Manuel Serrano, and Dr. Federico Pietrocola, now at the Karolinska Institutet, in Sweden, have studied how inducing senescence in cancer cells improves the effectiveness of the immune response to a greater degree than the dead cancer cells. After vaccinating healthy mice with senescent cancer cells and then stimulating the formation of tumours, the researchers observed that the animals did not develop cancer or that the number that do is significantly reduced. They also analysed the efficacy of vaccination in animals that had already developed tumours. In this setting, although the results were more moderate due to the protective barrier of the tumour, improvements were also observed.
"Our results indicate that senescent cells are a preferred option when it comes to stimulating the immune system against cancer, and they pave the way to considering vaccination with these cells as a possible therapy," explains Dr. Serrano, head of the Cellular Plasticity and Disease lab at IRB Barcelona.
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| Tags: cancer cells, ICREA, immune system, immunotherapy treatments, IRB Barcelona, Karolinska Institutet, melanoma, pancreatic cancer, senescence, tissue regeneration, tumors, vaccines
January 17, 2023
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Scientists from The Australian National University (ANU) and the Peter MacCallum Cancer Centre have discovered that a protein, called Menin, contributes to abnormal deactivation of specific genes in cancer cells.
One of the hallmarks of cancer is that the normal regulation of genes is disrupted, and this causes cancer cells to look and behave differently to normal cells. Cancer cells can switch off certain genes, keeping them in a dormant state. By deactivating specific immune genes, some cancers are able to evade detection by the immune system, essentially becoming invisible. This allows the cancer to grow and become more aggressive.
By targeting the Menin protein using drug therapies, the researchers believe they can reactivate these genes, making the cancer cells once again visible and allowing the immune system to seek out and destroy them.
The findings, published in Nature Cell Biology, could lead to new and more effective treatments for lymphoma and lung cancer.
Professor Mark Dawson, from the Peter MacCallum Cancer Centre, said the findings help scientists learn more about how cells function.
“Our research discovery has major implications for many different fields of research because we need to understand how cells make decisions and change the way they act in order to find new ways to treat cancer,” Professor Dawson said.
Source: https://www.anu.edu.au/
Categories: Uncategorized
| Tags: ANU, Australian National University, cancer cells, genes, immune system, invisible, lung cancer, lymphoma, Menin, protein
January 10, 2023
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In November 2022, Swiss scientists opened an eagerly awaited package from rural Ethiopia. It was full of shit. For two months, public health researcher Abdifatah Muhummed had been collecting stool samples from children in a remote, pastoralist community in Ethiopia’s Somali Region, as part of a global effort to catalog and preserve the diversity of human gut bacteria. He split each sample into four tubes, froze them at –80 degrees Celsius, and shipped two of them to Europe.
Trillions of bacteria, fungi, and other microbes live in the digestive tract. Many of them are beneficial to human health—influencing our metabolism and immune system, for example. But their diversity is under threat from industrialization, urbanization, and environmental changes. When Muhummed analyzed some of the samples he’d collected—culturing them in petri dishes and adding a dye to make them visible under a microscope—he was astounded to find signs of antibiotic resistance, even in samples taken from children who had never been exposed to modern antibiotics.
That’s one of the reasons scientists want to create a global biobank—a Noah’s ark of microbes, so to speak—and permanently store samples from around the world, before it’s too late. “Of course, it is difficult to concretely say what we are losing,” says microbiologist Adrian Egli, who is based in Zurich and is part of the launch team for the Microbiota Vault project.
Source: https://www.microbiotavault.org/
AND
https://www.wired.co.uk/
Categories: Uncategorized
| Tags: bacteria, digestive tract, diversity, fungi, global biobank, GUT, immune system, mass extinction, Microbiota Vault project, microbus, shit, stool
January 6, 2023
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Scientists at Brigham and Women’s Hospital (BWH) have found a way to fight cancer with cancer. The team genetically engineered cancer cells to release anti-cancer drugs at the site of established tumors, as well as stimulating the immune system against the disease. Tests in mice proved promising as both a therapy and a preventative vaccine.
Cancer vaccines are an emerging area of research, where patients are often administered inactive tumor cells or proteins expressed at high levels by cancer cells. This trains the immune system to recognize existing tumors and mount an assault on them, and can prevent the spread or appearance of new tumors. For the new study, the BWH team took a new approach, using living tumor cells instead.
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| Tags: Brigham and Women's Hospital, BWH, cancer, cancer vaccines, CRISPR, drugs, Glioblastoma, immune system, inactive tumor cells, living tumor cells, metastatic cancer, proteins, therapeutic tumor cells, ThTC, tumors, vaccine
December 19, 2022
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Immune checkpoint inhibitors such as Keytruda and Opdivo work by unleashing the immune system’s T cells to attack tumor cells. Their introduction a decade ago marked a major advance in cancer therapy, but only 10% to 30% of treated patients experience long-term improvement. In a paper published online today in The Journal of Clinical Investigation (JCI), scientists at Albert Einstein College of Medicine describe findings that could bolster the effectiveness of immune-checkpoint therapy. Rather than rally T cells against cancer, the Einstein research team used different human immune cells known as natural killer (NK) cells—with dramatic results.
“We believe the novel immunotherapy we’ve developed has great potential to move into clinical trials involving various types of cancer,” said study leader Xingxing Zang, M.Med., Ph.D., Professor of microbiology at Einstein and a member of the Cancer Therapeutics Program of the Montefiore Einstein Cancer Center.
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| Tags: Albert Einstein College of Medicine, cancer, cancer-cell protein, Einstein, Immune checkpoint inhibitors, immune system, immune-checkpoint therapy, Keytruda, KIR2DL5, monoclonal antibodies, natural killer, NK, NK cells, Opdivo, proteins, PVR, T-cells, TIGIT, tissue, tumor cells
November 30, 2022
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An experimental therapeutic cancer vaccine induced two distinct and desirable immune system responses that led to significant tumor regression in mice. This is according to a new research study published in the journal Cell, reported by investigators from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
According to the research findings, intravenous (IV) administration of the vaccine boosted the number of cytotoxic T cells capable of infiltrating and attacking tumor cells and engaged the innate immune system by inducing type I interferon. The innate immune response modified the tumor microenvironment, counteracting suppressive forces that otherwise would tamp down T-cell action. Modification of the tumor microenvironment was not found in mice that received the vaccine via subcutaneous administration (i.e. a needle injection into the skin).
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| Tags: cancer, cells, cytotoxic T cells, HPV, immune system, immunotherapeutic vaccines, IV, National Institute of Allergy and Infectious Diseases, National Institutes of Health, NIAID, NIH, papillomavirus, SNAPvax, tumor, type I interferon, Vaccine Research Center, Vaccitech North America, vax-innate, VRC
November 28, 2022
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With the help of an AI, researchers at Chalmers University of Technology, Sweden, have succeeded in designing synthetic DNA that controls the cells’ protein production. The technology can contribute to the development and production of vaccines, drugs for severe diseases, as well as alternative food proteins much faster and at significantly lower costs than today.
How our genes are expressed is a process that is fundamental to the functionality of cells in all living organisms. Simply put, the genetic code in DNA is transcribed to the molecule messenger RNA (mRNA), which tells the cell’s factory which protein to produce and in which quantities.
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| Tags: AI, cancer, cell, cell's protein, cell’s factory, Chalmers University of Technology, COVID-19, DNA, drugs, food proteins, gene expression, genes, genetic code, immune system, mRNA, mRNA vaccine, protein, protein-based drugs, RNA, severe diseases, synthetic DNA, vaccines, virus
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