March 21, 2023
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Scientists at ETH Zurich in Switzerland have made a breakthrough towards designing an off-the-shelf treatment for immunotherapy against cancer. A synthetic protein tweak can allow immune cells from any donor to be given to any patient without the risk of a dangerous immune reaction. Cancer patients might one day benefit from being administered immune cells from healthy donors. But as things stand, receiving donor cells can cause severe or even fatal immune reactions. A researcher at ETH Zurich has now developed a technology that avoids these.
Edo Kapetanovic is a medical doctor, but for a while now he has devoted himself entirely to research in synthetic immunology. He has completed his doctoral studies in immunoengineering and is working at the Department of Biosystems Science and Engineering at ETH Zurich in Basel. His big goal is to develop new cancer therapies by providing patients with immune cells derived from donor blood. He is now getting closer to this goal: he has managed to modify donor cells so that they attack only the tumour cells and not patient’s healthy cells. The technology has been tested in the lab in human cells, but it will take more time and development before the patients can benefit from the technology.
Administering donor cells is far from straightforward: the immune system is specialised in distinguishing foreign molecules from ‘self’ and will attack any foreign cell. This is particularly dangerous for immunocompromised patients, as donor cells can recognize patient cells as foreign and trigger a violent and, consequently, fatal immune response in the recipient, known as a graft-versus-host reaction. That is why today’s immunotherapeutic treatments for cancer mainly use a patient’s own immune cells rather than donated cells.
Kapetanovic and his team have now succeeded in engineering immune cells that are safe of graft-versus-host reaction. Generally speaking, approved immunotherapies for cancer take one of two approaches, and both depend on cells known as killer cells, mostly killer T cells. In one approach, experts extract the patient’s own killer cells and modify them in the lab so that they specifically recognise and eliminate cancer cells. These modified cells are then administered to the patient.
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Tags: bispecific antibodies, cancer, donor, ETH Zürich, graft-versus-host reaction, immune cells, immunoengineering, immunotherapy, killer T-cells, synthetic immunology, synthetic protein, synthetic TCR-CD3 complex, TCR-CD3
March 16, 2023
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Tumor cells typically alter their energy metabolism and increase glucose uptake to support their rapid division and spread. This limits glucose availability for immune cells and therefore dampens the body’s anti-cancer immune response. By searching for proteins that both regulate the metabolism of cancer cells and affect immune cells in tumors, a team led by investigators at Massachusetts General Hospital (MGH) recently identified a potential target for therapies that could simultaneously drain tumors of energy and boost the immune response against them.
For the research, which is published in Cancer Discovery, Keith T. Flaherty, MD, the director of Clinical Research at the MGH Cancer Center and a professor of medicine at Harvard Medical School, and his colleagues developed a new computational tool called BipotentR that can identify targets that block immune activation and also stimulate a second user-defined pathway (in this case, metabolism). When applied to gene expression data from patients with cancer who were treated with immunotherapy, as well as from cell lines and animal models, the tool identified 38 cancer cell–specific immune-metabolic regulators.
Artificial intelligence techniques showed that the activity level of these regulators in tumors predicted patients’ outcomes after receiving immunotherapy. The topmost identified regulator, ESRRA (Estrogen Related Receptor Alpha), was activated in immunotherapy-resistant tumors of many types. Inhibiting ESRAA killed tumors by suppressing energy metabolism and activating two immune mechanisms involving different types of immune cells.The scientists also demonstrated that BipotentR can be applied to other survival mechanisms used by cancer cells, such as their ability to promote blood vessel formation to increase their blood supply. Therefore, BipotentR, available at http://bipotentr.dfci.harvard.edu, provides a resource for discovering single drugs that can act through one cancer-related pathway while simultaneously stimulating an immune response.
Source: https://www.massgeneral.org/
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https://www.thebrighterside.news/
Categories: Uncategorized
| Tags: (Estrogen Related Receptor Alpha, AI, Artificial Intelligence, BipotentR, cancer, energy metabolism, ESRA, gene expression, Harvard Medical School, immune cells, immunity, immunotherapy, Massachusetts General Hospital, MGH, proteins, tumor cells
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
Categories: Uncategorized
| Tags: Alzheimer's, confusion, immune cells, immune system, memory loss, microglia, neurodegeneration, protein Tau, tauopathies, Washington University School of Medicine in St. Louis
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/
Categories: Uncategorized
| 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
December 26, 2022
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In a bit of “reverse engineering” research using brain tissues from five people who died with Alzheimer’s disease, Johns Hopkins Medicine researchers say they discovered that a special sugar molecule could play a key role in the development of Alzheimer’s disease. If further research confirms the finding, the molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments and perhaps prevention of Alzheimer’s disease, say the researchers. Alzheimer’s disease is the most common form of dementia in the United States. Affecting an estimated 5.8 million Americans, the progressive disorder occurs when nerve cells in the brain die due to the buildup of harmful forms of proteins called amyloid and tau.
Cleaning up the disease-causing forms of amyloid and tau is the job of the brain’s immune cells, called microglia. Earlier studies found that when cleanup is impaired, Alzheimer’s disease is more likely to occur. In some people, this is caused by an overabundance of a receptor on the microglia cells, called CD33.
“Receptors are not active on their own. Something needs to connect with them to block microglia from cleaning up these toxic proteins in the brain", says Ronald Schnaar, Professor of Pharmacology at the Johns Hopkins University School of Medicine and director of the laboratory that led the study. Past studies by the researchers showed that for CD33, these “connector” molecules are special sugars. Known to scientists as glycans, these molecules are ferried around the cell by specialized proteins that help them find their appropriate receptors. The protein-glycan combination is called a glycoprotein.
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| Tags: Alzheimer’s disease, amyloid, brain tissues, CD33, dementia, glycan, glycoprotein., immune cells, Johns Hopkins Medicine, microglia, molecule, nerve cells, proteins, receptors, RPTP zeta S3L, sialylated keratan sulfate, sugar, tau
December 16, 2022
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Teaching the body’s immune cells to recognize and fight cancer is one of the holy grails in medicine. Over the past two decades, researchers have developed new immunotherapy drugs that stimulate a patient’s immune cells to significantly shrink or even eliminate tumors. These treatments often focus on increasing the cancer-killing ability of cytotoxic T cells. However, these treatments appear to only work for the small group of patients who already have T cells within their tumors. One 2019 study estimated that under 13% of cancer patients responded to immunotherapy.
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| Tags: cancer, CAR-T cells, chimeric antigen receptor T cells, cytotoxic T cells, immune cells, immunotherapy drugs, nature, protein, receptor, San Francisco, solid tumors, synNotch, synthetic biology, synthetic Notch receptor, tumors, University of California
June 28, 2022
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In a bit of “reverse engineering” research using brain tissues from five people who died with Alzheimer’s disease, Johns Hopkins Medicine researchers say they discovered that a special sugar molecule could play a key role in the development of Alzheimer’s disease. If further research confirms the finding, the molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments and perhaps prevention of Alzheimer’s disease, say the researchers.
Alzheimer’s disease is the most common form of dementia in the United States. Affecting an estimated 5.8 million Americans, the progressive disorder occurs when nerve cells in the brain die due to the buildup of harmful forms of proteins called amyloid and tau.
Cleaning up the disease-causing forms of amyloid and tau is the job of the brain’s immune cells, called microglia. Earlier studies found that when cleanup is impaired, Alzheimer’s disease is more likely to occur. In some people, this is caused by an overabundance of a receptor on the microglia cells, called CD33.
A sugar molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments, and perhaps prevention of Alzheimer’s disease
“Receptors are not active on their own. Something needs to connect with them to block microglia from cleaning up these toxic proteins in the brain,” says Ronald Schnaar, Ph.D., the John Jacob Abel Professor of Pharmacology at the Johns Hopkins University School of Medicine and director of the laboratory that led the study.
Past studies by the researchers showed that for CD33, these “connector” molecules are special sugars. Known to scientists as glycans, these molecules are ferried around the cell by specialized proteins that help them find their appropriate receptors. The protein-glycan combination is called a glycoprotein.
The study was published online April 20 in the Journal of Biological Chemistry.
Source: https://www.hopkinsmedicine.org/
Categories: Uncategorized
| Tags: Alzheimer's, amyloid, CD33, cell, connector molecule, dementia, glycans, immune cells, Johns Hopkins University School of Medicine, microglia cells, protein, receptor, reverse engineering, sugar, tau
June 17, 2022
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Many cancer treatments are notoriously savage on the body; they attack healthy cells at the same time as tumor cells, causing a plethora of side effects. Now, researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have designed a method to keep one promising cancer drug from wreaking such havoc. The team has engineered a new “masked” version of the immunotherapy drug interleukin-12 that is activated only when it reaches a tumor.
Researchers have long suspected that interleukin-12 could be a powerful cancer treatment, but it caused dangerous side effects. Now, Pritzker Molecular Engineering researchers have developed a version of the molecule not activated until it reaches a tumor, where it eradicates cancer cells.
“Our research shows that this masked version of IL-12 is much safer for the body, but it possesses the same anti-tumor efficacy as the original,” said Aslan Mansurov, a postdoctoral research fellow and first author of the new paper. He carried out the IL-12 engineering work with Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering, who co-leads PME’s Immunoengineering research theme with professor Melody Swartz.
Researchers know that IL-12 potently activates lymphocytes, immune cells with the potential to destroy tumor cells. But, in the 1990s, early clinical trials of IL-12 were halted because of severe, toxic side effects in patients. The same immune activation that started a cascade of events killing cancer cells also led to severe inflammation throughout the body. IL-12, at least in its natural form, was shelved.
The research on the molecule, also known as IL-12, is described in the journal Nature Biomedical Engineering.
But Mansurov, Hubbell, Swartz, and colleagues had an idea to reinvigorate the possibility of IL-12. What if the drug could slip through the body without activating the immune system? They designed a “masked” molecule with a cap covering the section of IL-12 which normally binds immune cells. The cap can be removed only by tumor-associated proteases, a set of molecular scissors found in the vicinity of tumors to help them degrade surrounding healthy tissue. When the proteases chop off the cap, the IL-12 becomes active, able to spur an immune response against the tumor.
“The masked IL-12 is largely inactive everywhere in the body except at the site of the tumor, where these proteases can cleave off the mask,” explained Mansurov.
Source: https://pme.uchicago.edu/
Categories: Uncategorized
| Tags: cancer, drug, healthy cells, IL-12, immune cells, immunotherapy drug, interleukin-12, lymphocytes, molecule, PME, side effects, tumor, tumor cells, University of Chicago
June 2, 2022
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Activating the immune system at the site of a tumor can recruit and stimulate immune cells to destroy tumor cells. One strategy involves injecting immune-stimulating molecules directly into the tumor, but this method can be challenging for cancers that are not easily accessible. Now, Stanford researchers have developed a new synthetic molecule that combines a tumor-targeting agent with another molecule that triggers immune activation. This tumor-targeted immunotherapy can be administered intravenously and makes its way to one or multiple tumor sites in the body, where it recruits immune cells to fight the cancer.
Three doses of this new immunotherapy prolonged the survival of six of nine laboratory mice with an aggressive triple negative breast cancer. Of the six, three appeared cured of their cancer over the duration of the monthslong study. A single dose of this molecule induced complete tumor regression in five of 10 mice. The synthetic molecule showed similar results in a mouse model of pancreatic cancer.
An immunotherapy molecule administered intravenously to mice was shown to target tumors.
“We essentially cured some animals with just a few injections,” said Jennifer Cochran, PhD, the Shriram Chair of the Department of Bioengineering. “It was pretty astonishing. When we looked within the tumors, we saw they went from a highly immunosuppressive microenvironment to one full of activated B and T cells — similar to what happens when the immune-stimulating molecule is injected directly into the tumor. So, we’re achieving intra-tumoral injection results but with an IV deliver.”
A paper describing the study published online in Cell Chemical Biology. The lead authors are Stanford graduate student Caitlyn Miller and instructor of medicine Idit Sagiv-Barfi, PhD.
Source: https://med.stanford.edu/
Categories: Uncategorized
| Tags: aggressive triple negative breast cancer, cancers, immune cells, immune system, immunotherapy, molecules, Stanford, synthetic molecule, tumor cells
April 11, 2022
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After surgery to remove tumors, some cancer cells can be left behind where they can grow back or spread to a new part of the body. Researchers at the University of Wisconsin-Madison have now developed a hydrogel that can be applied post-surgery to prevent or slow tumor regrowth. The gel works by releasing two compounds selected to strategically keep cancer from coming back after surgery. First is a drug called Pexidartinib, which is already in use to inhibit tumor-associated macrophages (TAMs). These are immune cells that have, for unclear reasons, “switched sides” and now contribute to creating a pro-cancer environment. As such, inhibiting these TAMs slows the growth (or regrowth) of cancer.
A microscope image of the hydrogel (teal) containing platelets with antibodies (red) and tumor-fighting drug nanoparticles (green)
The second component is made up of PD-1 antibodies, which help train T cells to recognize and attack cancer cells. These are bound to platelets for stability. Together, the two components prevent the formation of a microenvironment that’s favorable to cancer growth, and help the immune system clear out any cancer cells remaining after surgery. After its work is done, the gel is designed to biodegrade safely in the body.
The researchers tested the gel in mouse models of several different types of cancers, including colon cancer, melanoma, sarcoma, and triple negative breast cancer. The gel significantly reduced recurrence and metastasis of the cancer, and extended the survival rates of the mice – all control animals succumbed within 36 days, while survival rates ranged between 50 and 66 percent for treated mice, depending on the type of cancer.
The local application of the gel also helps prevent side effects that can arise if a drug is delivered system-wide. As such, no major side effects were seen in the test mice. Importantly, the team says that some of these cancers don’t usually respond well to immune therapy, and are prone to metastasizing, so the effectiveness of the gel treatment is encouraging.
“We are really glad to see that this local strategy can work against so many different kinds of tumors, especially these non-immunogenic tumors,” said Quanyin Hu, lead researcher on the study. “We are even more glad to see this local treatment can inhibit tumor metastasis.”
Source: https://newatlas.com/
Categories: Uncategorized
| Tags: cancer, cancer cells, colon cancer, hydrogel, immune cells, melanoma, metastasis, PD-1 antibodies, Pexidartinib, sarcoma, T-cells, TAMs, triple negative breast cancer, tumor regrowth, tumor-associated macrophages, tumors, University of Wisconsin-Madison
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