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Low-cost cancer treatment with a device the size of a microwave



Low-cost cancer treatment with a device the size of a microwave

Low-cost cancer treatment with a device the size of a microwave. A Belgian biotech company is testing a device that produces cancer drugs in hospitals, reducing waiting times and the cost of treatment.

Low-cost cancer treatment with a device the size of a microwave

In this article we’re going to read about Low-cost cancer treatment with a device the size of a microwave. When cancer treatment with a chimeric antigen receptor T cell, or CAR-T, works, it can seem miraculous. About half of leukemia and lymphoma patients, and about a third of myeloma patients, get a complete cure with a single injection of immune T cells that have been genetically modified to find and kill cancer in the blood. CAR-T treatment for acute lymphoblastic leukemia, which is the most common type of childhood cancer, has shown a cure rate of up to 90%. The first two patients treated with CAR-T in 2010 were adult men suffering from end-stage acute lymphoblastic leukemia. They were still in remission a decade after treatment.

Since 2017, the US Food and Drug Administration (FDA) has approved a total of six CAR-T therapies, all for blood cancers. Many studies have been conducted with the aim of using CAR-T therapy on solid tumors, but none are yet at the clinical trial stage. Two of these treatments, known as “Yescarta” and “Tecartus”, have earned 1.5 billion dollars for Kite Pharma in 2022 alone. Until recently, CAR-T therapies were mainly considered a last resort for patients who have tried other drugs, but CAR-T therapy can be used earlier in the treatment process and is likely to have a big impact. Last year, Yescarta was approved as a second-line treatment for large B-cell lymphoma. Despite this, drug makers are currently facing a problem.

A survey conducted in 2022 by Mayo Clinic researchers found that the average time on the waiting list for CAR-T treatment was six months, and only a quarter of patients eventually received it. Another quarter was able to enter a clinical trial for treatments that have yet to be approved. In the past few years, Bristol Myers Squibb, Kite Pharma, and Novartis have all experienced manufacturing problems with their CAR-T therapies. Johnson & Johnson (J&J) and Legend Biotech (Legend Biotech) decided in March to stop launching their CAR-T therapy, Carvycti, in the UK due to production constraints.

Unlike conventional drugs, autologous CAR-T injections are living drugs that are customized for each patient. Blood sampling of patients is usually done in a hospital or special center. Once isolated, the T cells are shipped frozen to a biomanufacturing facility where they are genetically reprogrammed to express a tumor-seeking molecule called a chimeric antigen receptor (CAR) on their surface. The modified cells are placed in an incubator for days or weeks until their numbers increase enough to create a therapeutic dose. After several stages of quality testing, the modified CAR-T cells are frozen and returned to the hospital to be injected into the patient. This process usually takes a minimum of two weeks and a maximum of eight weeks.

Current CAR-T treatments cost between $300,000 and $400,000. Travis Young, vice president of the biology department at the non-profit California Biomedical Research Institute (Calibr), said: “The reason for the high cost of treatment is that the production process must be highly controlled at every point of it.” This requires a trained technician, clean rooms, and infrastructure for transportation and freezing. The most important time is pre-release testing to ensure product sterility and potency. There are many possibilities for problems. The supply chain is still in its infancy, and it’s not just about the infrastructure, it’s about the number of people who need to be trained to do the job.

Companies are tackling these challenges in a variety of ways, aiming to reduce the complexity, time, and cost of delivering CAR-T therapies to more patients. One of the more unlikely competitors is Belgium-based Galapagos NV, which last June announced a bold plan to produce these expensive treatments faster and more cost-effectively. The program proposes developing treatments not in a centralized location, but at the point of care, using a small automated device the size of a home microwave.

Galapagos had no prior experience with CAR-T therapy and had only marketed one product in Europe, the UK, and Japan since its inception in 1999. This product was the drug “Jyseleca” for the treatment of ulcerative colitis and rheumatoid arthritis, whose sales in 2022 were reported to be equal to 95 million dollars. The drug has recently undergone a series of clinical trials, but it has one special advantage: Paul Stoffels, the new CEO of Galapagos and former chief scientific officer of Johnson & Johnson.

When Stoffels left J&J at the end of 2021, he had one of the most enviable track records in the pharmaceutical industry. This Belgian-born doctor and specialist in infectious diseases during his training was in charge of the groups that produced 25 new drugs; including two successful cancer drugs, breakthrough treatments for HIV and tuberculosis, and vaccines for Ebola and Covid-19. Although Carvycti was approved a few months after Stoffels left, it was developed under his watch. During Stoffels’ tenure, J&J’s pharmaceutical sales more than doubled from $22.5 billion in 2009 to $45.6 billion in 2020. Seven of the drugs developed under Stoffels’ supervision have been added to the “World Health Organization’s” (WHO) list of essential drugs, which means that they are considered necessary to maintain health.

Stoffels’ stint in the Galapagos gives him the opportunity to demonstrate his ability in a larger company. Immediately after taking over as CEO last April, Stoffels orchestrated a major pivot, buying two startups working on different aspects of CAR-T therapies and manufacturing them, and four months later hired 200 people working on drug programs. They were working older, fired.

Galapagos sets up manufacturing units at each of its partner hospitals, which includes training people, installing equipment, and validating the manufacturing process, Stoffels explained about the process. This is a new approach but much simpler than centralized manufacturing. In centralized manufacturing, you have to invest several hundred million dollars in a building, hire between 500 and 1,000 people, train them, and produce the drug there, but for us, the heavy lifting of this technology has already been done.

From a biological perspective, using diseased cells that have never been frozen has advantages that affect cell health. Newly generated CAR-T cells, after re-injection into the patient, show robust and consistent growth, which helps minimize a common side effect of CAR-T therapy called cytokine release syndrome, Stoffels continued. This syndrome is an aggressive reaction to immunotherapy that causes fever, nausea, and fatigue. The fact that the treatment can be done in seven days allows people with a very short life expectancy to receive this type of treatment. The first patient treated with CAR-T, who came to the hospital with acute respiratory distress syndrome and severe tumor recurrence, is still in excellent condition. This could never have been done with CAR-T the old way and in one centralized location.

Read More: Scientists discovered the secret of DNA’s X shape

Decentralization, simplification, and automation of the entire process will significantly reduce CAR-T costs, Stoffels added. The time required and the amount of work that needs to be done make CAR-T treatments expensive. If you put four or five systems in a hospital room, you can treat 200 patients a year using only a small staff.

Galapagos will not be immune to shortages of chemical reagents and other raw materials that affect other companies. “All the challenges are compounded by not having trained technicians to do the work,” Travis Young said. Technicians don’t need a lot of training because the systems require a lot less manipulation, but whenever you distribute these systems across hospital centers, you lose some control over them all.

After all, Stoffels has made the impossible possible before, and he’s done it many times, and he doesn’t seem to be giving up. He added: “I have worked all my life trying to get access to medicines.” This work is also such a mission. New science allows us to do new, difficult, and different things, and if you don’t start, you will never reach the goal.



Making a small version of the intestine in the laboratory




Making a small version of the intestine in the laboratory

Making a small version of the intestine in the laboratory. A lab-grown small intestine could help provide personalized treatment for Crohn’s disease.

Making a small version of the intestine in the laboratory

Scientists have found a way to reveal the severity of intestinal diseases through epigenetic changes, which could help develop a new treatment plan for patients.

For decades, biomedical researchers have been looking for ways to develop a standard treatment for patients with Crohn’s disease and irritable bowel disease (IBD).

Now, scientists at the University of Cambridge have discovered a way to grow a small intestine in the lab from cells taken from a patient for more precise and personalized treatments.

Professor Matthias Zilbauer, professor of pediatric gastroenterology at the University of Cambridge and Cambridge University Hospitals, explained: “The actual model of this small intestine was made more than a decade ago by a scientist named Hans Clovers. Together with a group of scientists, he discovered structural units called intestinal epithelial stem cells.

He added that the scientists combined this with what is needed for cells to continue growing and dividing after they leave the gut.

Focusing on children with Crohn’s disease

Inspired by this model that grows organoids from humans, researchers in this new study found specific epigenetic findings in patients, especially children and adolescents, with Crohn’s disease.

Crohn’s disease is a chronic inflammatory bowel disease whose cases are increasing worldwide, especially among children. This disease significantly affects the quality of life of patients and can lead to severe complications.

A new pathway called major histocompatibility complex class I (MHC class I) was observed, which appears to be regulated by changes in epigenetic programming.

Scientists have discovered a way to reveal the severity of diseases through epigenetic changes, which could help develop a new treatment plan for patients.

“What we found was that patients with significant epigenetic changes had a more severe disease course,” says Seelbauer.

Drug treatment for the small intestine in vitro before administration to the patient

Scientists hope to develop new drugs that can be tested on this small lab intestine before being given to a patient.

Conventional treatments are only effective 60% of the time, so the vast majority of patients may not respond to them and may even be exposed to severe side effects.

In the future, scientists hope to grow these organoids from patients for drug testing and, if a drug works on the small intestine, administer it to the patient.

The study found that the cells that make up the inner lining of the intestine in patients with Crohn’s disease show increased activity of major histocompatibility complex class I, which are proteins found on the surface of nearly all nucleated cells in the body and are critical for the immune response.

Read more: Artificial intelligence identifies cancer killer cells

This high activity can lead to inflammation by activating immune cells to more easily recognize antigens such as toxins or other foreign substances. Antigens may include molecules from food or gut microbiota that trigger an immune response and contribute to the inflammation characteristic of Crohn’s disease. This is the first time that stable epigenetic changes have been shown to explain intestinal epithelial abnormalities in Crohn’s patients.

The team of researchers is currently working on finding drugs that can modify this pathway.

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How to rejuvenate an aging immune system?




immune system
Scientists succeeded in rejuvenating the immune system of old mice with a new therapeutic approach.

How to rejuvenate an aging immune system?

After scientists reduced abnormal stem cells in old animals, mice’s immune systems became more youthful. This technique enhanced the response of old rodents to viral infection and reduced signs of inflammation. In this method, published March 27 in the journal Nature, old mice are treated with an antibody to reduce a population of stem cells that give rise to other types of cells, such as those involved in inflammation.

Excessive inflammation can wreak havoc on the body, and pro-inflammatory stem cells proliferate during aging in mice and humans.

Imbalanced immune system

For decades, researchers in Irving Weissman’s group at Stanford University in California have closely followed the fate of blood stem cells. These cells replenish the supply of red blood cells (which carry oxygen from the lungs to all parts of the body) and white blood cells (which are key components of the immune system).

Balancing the blood stem cell population can rejuvenate the immune system

In 2005, Weissman and colleagues found that as mice age, their blood stem cell population changes. In young mice, there is a balance between two types of blood stem cells, each contributing to a different branch of the immune system. The adaptive compartment produces antibodies and T cells that target specific pathogens. The innate part produces general responses such as inflammation against infection.

However, in old mice, the balance between the two parts of the immune system is skewed towards the production of more pro-inflammatory innate immune cells. Similar changes have been reported in the blood stem cells of aging humans, and researchers speculate that this could lead to a reduced ability to produce new antibodies and T-cell responses. This may explain why the elderly are more susceptible to serious infections from pathogens such as influenza viruses and SARS-CoV-2, and why their response to vaccination is weaker than that of younger people.

Restore the balance of the immune system

If the researchers’ conclusions are correct, restoring balance to the blood stem cell population could also rejuvenate the immune system.

The researchers tested this hypothesis by producing antibodies that bind to blood stem cells, which mainly produce innate immune cells. They then injected these antibodies into old mice with the hope that their immune systems would destroy the stem cells attached to the antibodies.

Antibody treatment rejuvenated the immune system of treated mice. They showed a stronger reaction to the vaccination than the old mice that did not receive the treatment and were better at warding off the viral infection. The treated mice also had lower levels of proteins associated with inflammation, which the authors say shows how different populations of blood stem cells affect the aging of the immune system.

It is possible that the effect of antibody treatment is more than affecting the blood stem cell population. Antibody therapy may also affect the environment in which blood stem cells can live. On the other hand, the said treatment can clear other old cells from the body or stimulate immune responses, thus affecting how mice respond to vaccines and viruses.

It will be years before Weissman and his colleagues’ approach can be tested in humans, but many aspects of the stem cell biology that underlies the production of immune cells are similar in mice and humans.

Weissman’s team is working on a similar approach to rebalance the blood stem cells of elderly people. He believes that even if there is sufficient funding and no unexpected obstacles arise, it will take at least three to five years before they can test their method on humans. In the meantime, the researchers will continue to study the mice to learn more about other effects of the antibody therapy, such as whether it affects the rate of cancer or inflammatory diseases. “The blood-forming system of young and old blood is very different,” says Weissman. “The difference is not just in the bone marrow, but throughout the body.”

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How can hacking the immune system help slow aging?




immune system
Our immune system weakens over time and this could explain the negative effects of aging. Manipulation of the immune system may alter the aging process.

How can hacking the immune system help slow aging?

Stem cell researcher Carolina Florian couldn’t believe what she was seeing. His old laboratory mice began to look younger. They were more lively and their fur was shinier. However, all he had done was a short treatment a few weeks earlier with a drug that modified the organization of proteins in a type of stem cell.

Stem cell researcher Carolina Florian couldn’t believe what she was seeing. His old laboratory mice began to look younger. They were more lively and their fur was shinier. However, all he had done was a short treatment a few weeks earlier with a drug that modified the organization of proteins in a type of stem cell.

When technicians repeating Florian’s experiment in two other laboratories reached the same conclusion, Florian became more confident that the treatment in question would rejuvenate the animals. In two papers in 2020 and 2022, his team explained how this process extended the lifespan of mice and kept them in good physical condition into old age.

The purpose of Florian Elixir is the immune system. The immune cells he targeted are called hematopoietic stem cells, which give rise to mature immune cells. By circulating the blood, a mixture of these cells enters all the organs and affects all the functions of the body. However the molecular composition of hematopoietic stem cells changes during aging, and this upsets the balance of the immune cells that these stem cells produce.

Florian, who works at the Bleuge Biomedical Research Institute in Barcelona, ​​says reversing the misalignment that occurs over time appears to reverse many of the problems of aging, not only in the immune system but in the rest of the body as well.

Health and agingDescription Researchers think the immune system could be the key to healthy aging.

In a paper published in March in the journal Nature, researchers show that restoring the balance between two key types of immune cells rejuvenates the immune system of aging mice and improves the animals’ ability to respond to vaccines and ward off viral infections.

Other scientists have used different experimental methods to reach a similar conclusion: Rejuvenating the immune system rejuvenates many organs in animals, at least in mice. More interestingly, evidence shows that aging of the immune system may cause aging of those organs.

The potential of the findings to help people stay healthy in old age is tantalizing. But applying this knowledge and using it in clinics will be challenging. Tampering with the immune system can be dangerous. Therefore, researchers initially aimed at low-risk goals such as improving the response of the elderly to vaccination and improving the efficacy of cancer immunotherapy.

Vittorio Sebastiano, a stem cell scientist at the Stanford School of Medicine in California, says the prospect that reversing aging might curb age-related diseases is enticing, but we proceed with caution.

Weakened immunity

The human immune system is a complex system whose many cellular and molecular components work together to help a person grow, protect him from infection, help heal wounds, and destroy cells that are becoming cancerous. But along with aging and changing the composition of the system, its efficiency decreases. In old age, people become susceptible to a wide range of infectious and non-infectious diseases and become more resistant to the protective power of vaccines.

Aging of the immune system may cause aging of different body parts

The immune system has two main components: the innate system, which indiscriminately destroys invading pathogens, and the more precise adaptive immune system, whose components learn to recognize and produce antibodies against specific foreign bacteria and viruses.

Hematopoietic stem cells in the bone marrow produce both arms of the immune system. They differentiate into two main types (lymphoid cells and myeloid cells), which then undergo further differentiation.

Lymphoid cells are primarily responsible for adaptive immunity and include B cells that produce antibodies, T cells that help attack invaders and coordinate immune responses and natural killer cells that kill infectious cells. Myeloid cells comprise a group of cell types that are mainly involved in innate immunity.

protein inside cellsProteins in stem cells that produce immune cells become more symmetrical as they age (right).

One of the first changes in the immune system during aging is the shrinking of the thymus, which begins after puberty. The thymus is where T cells mature, but much of this tissue turns to fat by the third decade of life, reducing the production of new T cells and weakening the immune system.

In addition, the function of T cells changes with age and they are not as specialized in detecting infectious agents as before. The ratio of different types of immune cells in the circulation also changes. The ratio of myeloid to lymphoid cells is significantly skewed toward myeloid cells and this can cause inflammation. In addition, an increasing number of immune cells become senescent, meaning that they stop replicating but do not die.

Aging cells usually occur when they undergo mutations. When cells are in this condition, they begin to release inflammatory signals and mark themselves for destruction.

An important anti-cancer and wound-healing mechanism works best when young. But when too much damage accumulates with age and the immune cells themselves age, this mechanism is disrupted. Senescent immune cells, attracted by inflammatory signals from senescent tissues, secrete their own inflammatory molecules. Therefore, they are not cleared properly but instead, add to the inflammation that also damages the surrounding healthy tissues. This phenomenon is known as inflammatory aging. This turns into a terrible positive feedback loop, says Aran Akbar, an immunologist at University College London. Evidence shows that this feedback loop is initiated by the immune system.

Laura Niedernhofer from the University of Minnesota in Minneapolis has shown in a series of experiments in mice that the aging of immune cells causes the aging of other tissues. He says these cells are very dangerous.

His team used genetic methods to delete an important DNA repair enzyme in the immune system of mice. The animals remained healthy until adulthood, but after that, they were no longer able to correct the accumulated mutations, and different types of immune cells began to age.

A few months later, an increasing number of cells in organs such as the liver and kidney were also senescent, and signs of organ damage appeared. When the scientists gave old mice immune cells from the spleens of young, healthy mice, all of these effects were reversed. All of this suggests that modifying the aging properties of the immune system could help prevent or reduce age-related diseases, Niederenhofer says.

Fight against aging

Many scientists are trying to do this from very different angles. Many approaches suggest that very short treatment of the immune system may have long-term effects and minimize side effects.

One of the ways to deal with aging immune cells is to use drugs to remove or inhibit the inflammatory factors that these cells release. Aging immune cells in humans can be changed, Niederenhofer says. If you smoke, they increase and if you exercise, they decrease.

Modifying the immune system can help prevent or reduce aging-related diseases

Some drugs, such as dasatinib, which is approved for the treatment of certain cancers, and quercetin, which is marketed as an antioxidant dietary supplement but not approved as a drug, slow cellular aging, and several trials are testing their effects on aging-related diseases.

Niederneuhofer is conducting a small clinical trial in elderly people with sepsis. Sepsis is a condition that becomes more deadly with age. His team is also conducting experiments to assess which types of immune cells are most involved in aging in the body, and their results could help design more precise treatments. Two types of cells (T cells and natural killer cells) are emerging as the main contenders, he says. He plans to examine natural products and approved drugs for their ability to interact with these types of immune cells during aging.

Akbar thinks targeting inflammation may be just as effective as targeting senescent cells. He and his colleagues conducted a study in healthy volunteers using the investigational compound lozepimod, which inhibits an enzyme involved in the production of a type of inflammatory molecule called cytokines. They treated volunteers with this drug for four days and then measured their skin’s response to an injection of the chickenpox virus over the course of a week. Most people are exposed to this virus during their life and this virus often stays in the body.

As people age, they lose their immunity to the chicken pox virus, and this time it can appear as shingles. The drug restored the immune response in the skin of older volunteers to a level similar to that of young volunteers. Akbar has found in unpublished studies that the same strong results persist up to three months later. Temporarily inhibiting inflammation in this way to keep the immune system functioning may similarly enhance the response of older patients to flu vaccinations, he says.

Boosting the immune system

The value of priming the elderly immune system prior to vaccination has been demonstrated in a series of clinical trials led by Joanne Mannick, CEO of Boston, Massachusetts-based Tornado Therapeutics. The trials tested analogs of the drug rapamycin and other drugs with similar mechanisms that target the immune system and are approved to prevent organ transplant rejection and to treat certain cancers.

The mentioned drugs inhibit an enzyme called mTOR, which is vital for many physiological functions and whose function is impaired in aging. Participants were treated with doses of the drug that were low enough to avoid side effects for several weeks before receiving the flu vaccine. This treatment regimen improved their response to the vaccine and increased their immune system’s ability to resist viral infections.

vaccinationVaccines are less effective in older people, but new approaches could increase their potency.

However the drug rapamycin can increase susceptibility to infection and affect metabolism, so Manick is planning trials with similar drugs that could be safer. “There are different ways to improve the immune system,” he notes.

Another way is to try to restore thymus function to maintain the production of new T cells. Jarrod Dudakoff, an immunologist at the Fred Hutchinson Cancer Center in Seattle, is studying the basic biology of thymus cells to understand how they regenerate after bouts of stress. Dudakov says it’s a little early to see how our understanding of this can be applied in the clinic. But he thinks it’s important to preserve the ability of the thymus to produce T cells.

Others try to fight aging by producing thymus tissue from powerful stem cells and then transplanting it. But Greg Fahey, chief scientific officer at Intervene Immune in Torrance, Calif., says there’s no need to wait to achieve those long-term prospects because synthetic growth hormone regenerates thymus tissue. He is conducting small studies in healthy volunteers using growth hormones as part of a mixture of compounds.

Preliminary results show that the amount of functional thymus tissue in the participants increased and their epigenetic clock (a biomarker of aging) was reversed by several years. Fahey is conducting further testing to see if the drug combination also improves the physical condition of the participants.

Turn back the clock

Another approach that has yet to reach the clinic is reprogramming immune cells to try to turn back the clock on cells that have aged. This procedure involves temporarily placing the cells in a dish exposed to a combination of transcription factors that induce a pluripotent state in mature cells.

Sebastiano and colleagues have shown in human cells that this corrects the epigenetic changes that accompany aging. He has founded a startup to use this technique to tackle a type of cancer treatment called CAR T, in which T cells are engineered outside the body to target and destroy a person’s cancer. However, the T cells may age before they are returned to the person. Rejuvenating them makes production faster and more powerful, says Sebastiano.

One of the challenges of aging studies is the inability to measure aging accurately

Florian’s approach also aims to produce healthier immune cells within the body. Hematopoietic stem cells in the blood develop epigenetic changes and their environment also changes with age. This causes the proteins to arrange themselves in a more symmetrical way in the cells (a process known as polarization), which shifts the balance of differentiation of stem cells towards myeloid cells.

In his studies, Florian used a four-day treatment with a compound called CASIN, which inhibited part of this process to correct polarization and help the mice live longer. When hematopoietic stem cells from aged mice that had received CASIN were transplanted into aged mice that had not received the treatment, the same life-extending effects were seen. Florian hopes to turn his results into a practical method in the clinic. He thinks his drug may help rebuild the immune system after receiving cancer chemotherapy.

The challenge of measuring aging

Research on immune aging faces major challenges. One of the challenges in aging studies of all organs is the inability to measure aging accurately. “We don’t know in a quantitative, measurable, predictable way what aging means at the molecular level in different cell types,” says Sebastiano. “Without these metrics, it is very difficult to demonstrate rejuvenation.”

Another challenge is the difficulty in determining the characteristics that make an immune cell unique. Until recently, it was difficult to show where each of the immune cell subsets lived and how they changed over time. But technologies such as single-cell RNA sequencing, which quantitatively measures genes expressed in single cells, have made the analysis more challenging. For example, a large study of immune cells in the blood of humans and mice across a range of ages, published last November, revealed 55 subpopulations. Only 12 subpopulations of cells changed with age.

By collaborating with different research areas, scientists hope to prove that the immune system plays an important role in healthy aging. Don’t expect an elixir of youth anytime soon, says Florian. Aging research will take a long time, but it can help design tools that will be transformative.

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