The Power of Stem Cells | California’s Stem Cell Agency

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Stem cells have the potential to treat a wide range of diseases. Here, discover why these cells are such a powerful tool for treating diseaseand what hurdles experts face before new therapies reach patients.

How can stem cells treat disease? What diseases could be treated by stem cell research? How can I learn more about CIRM-funded research in a particular disease? What cell therapies are available right now? When will therapies based on embryonic stem cells become available? What about the therapies that are available overseas? Why does it take so long to create new therapies? How do scientists get stem cells to specialize into different cell types? How do scientists test stem cell therapies? Can’t stem cell therapies increase the chances of a tumor? Is there a risk of immune rejection with stem cells? How do scientists grow stem cells in the right conditions?

When most people think about about stem cells treating disease they think of a stem cell transplant.

In a stem cell transplant, embryonic stem cells are first specialized into the necessary adult cell type. Then, those mature cells replace tissue that is damaged by disease or injury. This type of treatment could be used to:

But embryonic stem cell-based therapies can do much more.

Any of these would have a significant impact on human health without transplanting a single cell.

In theory, theres no limit to the types of diseases that could be treated with stem cell research. Given that researchers may be able to study all cell types via embryonic stem cells, they have the potential to make breakthroughs in any disease.

CIRM has created disease pages for many of the major diseases being targeted by stem cell scientists. You can find those disease pages here.

You can also sort our complete list of CIRM awards to see what we’ve funded in different disease areas.

Many clinical trials for embryonic stem cell-based therapies have begun in recent months. Results from those won’t be available until the trials reveal that the therapies are safe and effectivewhich could take a few years.

The only stem cell-based therapy currently in use is in bone marrow transplantation. Blood-forming stem cells in the bone marrow were the first stem cells to be identified and were the first to be used in the clinic. This life-saving technique has helped thousands people worldwide who had been suffering from blood cancers, such as leukemia.

In addition to their current use in cancer treatments, research suggests that bone marrow transplants will be useful in treating autoimmune diseases and in helping people tolerate transplanted organs.

Other therapies based on adult stem cells are currently in clinical trials. Until those trials are complete we won’t know which type of stem cell is most effective in treating different diseases.

There is no way to predict when the first human embryonic stem cell therapies will become widely available. Several applications with the FDA to begin human trials of embryonic stem cell-based therapies have been approved. In general, the path from the first human trial to widespread use is on the order of a decade. That long time frame is a result of the many steps a therapy must go through in order to show that it is both safe and effective. Only once those steps are complete will the FDA approve the therapy for general use.

If embryonic stem cells follow a normal path it could still be many years before therapies based on embryonic stem cells are widely available. However, if researchers gave up on therapies simply because the path towards FDA approval is long, we would not have any of the lifesaving technologies that are now commonplace: recombinant insulin, bone marrow transplantation or chemotherapy drugs.

Find Out More: Read the top ten things to know about stem cell treatments (from ISSCR) Alan Lewis talks about getting an embryonic stem cell-based therapy to patients (3:46)

Many overseas clinics advertise miraculous stem cell therapies for a wide range of incurable diseases. This phenomenon is called stem cell tourism and is currently a source of concern for reputable stem cell scientists. International (and even domestic) clinics are offering up therapies that have not been tested for safety or even for effectiveness. In the past few years, some patients who visited those clinics have died as a result of receiving unproven, untested stem cells.

Find Out More: Learn more about the issue on our StemCell Tourism page. Jeanne Loring discusses concerns about stem cell tourism (3:38) CIRM/ISSCR panel on stem cell tourism

Embryonic stem cells hold the potential to treat a wide range of diseases. However, the path from the lab to the clinic is a long one. Before testing those cells in a human disease, researchers must grow the right cell type, find a way to test those cells, and make sure the cells are safe in animals before moving to human trials.

Find Out More: Hans Keirstead talks about hurdles in developing a new therapy (5:07)

One of the biggest hurdles in any embryonic stem cell-based therapy is coaxing stem cell to become a single the cell type. The vital process of maturing stem cells from a pluripotent state to an adult tissue type is called differentiation.

Guiding embryonic stem cells to become a particular cell type has been fraught with difficulty. Normally, stem cells growing in a developing embryo receive a carefully choreographed series of signals from the surrounding tissue. In a lab dish, researchers have to mimic those signals. Add the signals in the wrong order or the wrong dose and the developing cells may choose to remain immatureor become the wrong cell type

Many decades of research has uncovered many of the signals needed to properly differentiate cells. Other signals are still unknown. Many CIRM-funded researchers are attempting to differentiate very pure populations of mature cell types that can accelerate therapies.

Find Out More: Mark Mercola talks about differentiating cells into adult tissues (3:37)

Once a researcher has a mature cell type in a lab dish, the next step is to find out whether those cells can function in the body. For example, embryonic stem cells that have matured into insulin-producing cells in the lab are only useful if they continue producing insulin once transplanted inside a body. Likewise, researchers need to know that the cells can integrate into the surrounding tissue.

Scientists test cells by first developing an animal model that mimics the human disease, and then implanting the cells to see if they help treat the disease. These types of experiments can be painstakingbecause even if the cells dont completely cure the disease, they may restore some functions that would still be of enormous benefit to people. Researchers have to examine each of these possible outcomes.

In many cases testing the cells in a single animal model doesnt provide enough information. Most animal models of disease dont perfectly mimic the human disease. For example, a mouse carrying the same mutation that causes cystic fibrosis in humans doesnt show the same signs as a person with the disease. So, a stem cell therapy that treats this mouse model of cystic fibrosis may not work in humans. Thats why researchers often need to test the cells in many different animal models.

The promise of embryonic stem cells is that they can form any type of cell in the body. The trouble is that when implanted into an animal they do just that, in the form of tumors called teratomas. These tumors consist of a mass of many cells types and can include hair cells and many other tissues.

These teratomas are one reason why it is necessary to mature the embryonic stem cells into highly purified adult cell types before implanting into humans. Virtually all evidence has shown that the mature cells are restricted to their one identity and dont appear to revert to a teratoma-forming cell.

Find Out More: UC Davis researcher focuses on stem cell safety (from UC Davis) Paul Knoepfler talks about the tendency of embryonic stem cells to form tumors (4:10)

Transplanted stem cells, like any transplanted organ, can be recognized by the immune system as foreign and then rejected. In organ transplants such as liver, kidney, or heart, people must be on immune suppressive drugs for the rest of their lives to prevent the immune system from recognizing that organ as foreign and destroying it.

The likelihood of the immune system rejecting a transplant of embryonic stem cell-based tissue depends on the origin of that tissue. Stem cells isolated from IVF embryos will have a genetic makeup that will not match that of the person who receives the transplant. That persons immune system will recognize those cells as foreign and reject the tissue unless a person is on powerful immune suppressive drugs.

Stem cells generated through SCNT or iPS cell technology, on the other hand, are a perfect genetic match. The immune system would likely overlook that transplanted cells, seeing it as a normal part of the body. Still, some suggest that even if the cells are perfectly matched, they may not entirely escape the notice of the immune system. Cancer cells, for example, have the same genetic make up as surrounding tissue and yet the immune system will often identify and destroy early tumors. Until more information is available from animal studies it will be hard to know whether transplanted patient-specific cells are likely to call the attention of the immune system.

Find Out More: Jeffrey Bluestone talks about immune rejection of stem cell-based therapies (4:05)

In order to be approved by the FDA for use in human trials, stem cells must be grown in good manufacturing practice (GMP) conditions. Under GMP standards, a cell line has to be manufactured so that each group of cells is grown in an identical, repeatable, sterile environment. This ensures that each batch of cells has the same properties, and each person getting a stem cell therapy gets an equivalent treatment. Although the FDA hasnt yet issued guidelines for how pluripotent stem cells need to meet GMP standards, achieving this level of consistency could mean knowing the exact identity and quantity of every component involved in growing the cells.

Growing stem cells under strictly controlled conditions is still a challenge. Most stem cells are grown on feeder cells, a layer of animal or human cells on the lab dish that provide the nutrients the cells need to grow and divide. Scientists dont currently know what it is exactly that the feeder cells provide, and so the use of those feeder cells probably wont conform to GMP standards. CIRM is funding researchers who are trying to learn how to grow pluripotent stem cell lines in the absence of feeder cells, and to isolate new lines under GMP standards.

Updated 1/15

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The Power of Stem Cells | California’s Stem Cell Agency

Gene Therapy Successes – Learn Genetics

Researchers have been working for decades to bring gene therapy to the clinic, yet very few patients have received any effective gene-therapy treatments. But that doesn’t mean gene therapy is an impossible dream. Even though gene therapy has been slow to reach patients, its future is very encouraging. Decades of research have taught us a lot about designing safe and effective vectors, targeting different types of cells, and managing and minimizing immune responses in patients. We’ve also learned a lot about the disease genes themselves. Today, many clinical trials are underway, where researchers are carefully testing treatments to ensure that any gene therapy brought into the clinic is both safe and effective.

Below are some gene therapy success stories. Successes represent a variety of approachesdifferent vectors, different target cell populations, and both in vivo and ex vivo approachesto treating a variety of disorders.

Sebastian Misztal was a patient in a hemophilia gene therapy trial in 2011. Following the treatment, Misztal no longer had spontaneous bleeding episodes. Credit: UCLH/UCL NIHR Biomedical Research Centre

Several inherited immune deficiencies have been treated successfully with gene therapy. Most commonly, blood stem cells are removed from patients, and retroviruses are used to deliver working copies of the defective genes. After the genes have been delivered, the stem cells are returned to the patient. Because the cells are treated outside the patient’s body, the virus will infect and transfer the gene to only the desired target cells.

Severe Combined Immune Deficiency (SCID) was one of the first genetic disorders to be treated successfully with gene therapy, proving that the approach could work. However, the first clinical trials ended when the viral vector triggered leukemia (a type of blood cancer) in some patients. Since then, researchers have begun trials with new, safer viral vectors that are much less likely to cause cancer.

Adenosine deaminase (ADA) deficiency is another inherited immune disorder that has been successfully treated with gene therapy. In multiple small trials, patients’ blood stem cells were removed, treated with a retroviral vector to deliver a functional copy of the ADA gene, and then returned to the patients. For the majority of patients in these trials, immune function improved to the point that they no longer needed injections of ADA enzyme. Importantly, none of them developed leukemia.

Gene therapies are being developed to treat several different types of inherited blindnessespecially degenerative forms, where patients gradually lose the light-sensing cells in their eyes. Encouraging results from animal models (especially mouse, rat, and dog) show that gene therapy has the potential to slow or even reverse vision loss.

The eye turns out to be a convenient compartment for gene therapy. The retina, on the inside of the eye, is both easy to access and partially protected from the immune system. And viruses can’t move from the eye to other places in the body. Most gene-therapy vectors used in the eye are based on AAV (adeno-associated virus).

In one small trial of patients with a form of degenerative blindness called LCA (Leber congenital amaurosis), gene therapy greatly improved vision for at least a few years. However, the treatment did not stop the retina from continuing to degenerate. In another trial, 6 out of 9 patients with the degenerative disease choroideremia had improved vision after a virus was used to deliver a functional REP1 gene.

Credit: Jean Bennett, MD, PhD, Perelman School of Medicine, University of Pennsylvania; Manzar Ashtari, Ph.D., of The Children’s Hospital of Philadelphia, Science Translational Medicine.

People with hemophilia are missing proteins that help their blood form clots. Those with the most-severe forms of the disease can lose large amounts of blood through internal bleeding or even a minor cut.

In a small trial, researchers successfully used an adeno-associated viral vector to deliver a gene for Factor IX, the missing clotting protein, to liver cells. After treatment, most of the patients made at least some Factor IX, and they had fewer bleeding incidents.

Patients with beta-Thalassemia have a defect in the beta-globin gene, which codes for an oxygen-carrying protein in red blood cells. Because of the defective gene, patients don’t have enough red blood cells to carry oxygen to all the body’s tissues. Many who have this disorder depend on blood transfusions for survival.

In 2007, a patient received gene therapy for severe beta-Thalassemia. Blood stem cells were taken from his bone marrow and treated with a retrovirus to transfer a working copy of the beta-globin gene. The modified stem cells were returned to his body, where they gave rise to healthy red blood cells. Seven years after the procedure, he was still doing well without blood transfusions.

A similar approach could be used to treat patients with sickle cell disease.

In 2012, Glybera became the first viral gene-therapy treatment to be approved in Europe. The treatment uses an adeno-associated virus to deliver a working copy of the LPL (lipoprotein lipase) gene to muscle cells. The LPL gene codes for a protein that helps break down fats in the blood, preventing fat concentrations from rising to toxic levels.

Several promising gene-therapy treatments are under development for cancer. One, a modified version of the herpes simplex 1 virus (which normally causes cold sores) has been shown to be effective against melanoma (a skin cancer) that has spread throughout the body. The treatment, called T-VEC, uses a virus that has been modified so that it will (1) not cause cold sores; (2) kill only cancer cells, not healthy ones; and (3) make signals that attract the patient’s own immune cells, helping them learn to recognize and fight cancer cells throughout the body. The virus is injected directly into the patient’s tumors. It replicates (makes more of itself) inside the cancer cells until they burst, releasing more viruses that can infect additional cancer cells.

A completely different approach was used in a trial to treat 59 patients with leukemia, a type of blood cancer. The patients’ own immune cells were removed and treated with a virus that genetically altered them to recognize a protein that sits on the surface of the cancer cells. After the immune cells were returned to the patients, 26 experienced complete remission.

Patients with Parkinson’s disease gradually lose cells in the brain that produce the signaling molecule dopamine. As the disease advances, patients lose the ability to control their movements.

A small group of patients with advanced Parkinson’s disease were treated with a retroviral vector to introduce three genes into cells in a small area of the brain. These genes gave cells that don’t normally make dopamine the ability to do so. After treatment, all of the patients in the trial had improved muscle control.

Excerpt from:

Gene Therapy Successes – Learn Genetics

Gene Therapy – Biotechnology – Science and Research

Gene therapy is using “genes as medicine”. It is an experimental approach to treating genetic disease where the faulty gene is fixed, replaced or supplemented with a healthy gene so that it can function normally. Most genetic diseases cannot be treated, but gene therapy research gives some hope to patients and their families as a possible cure. However, this technology does not come without risks and many clinical trials to evaluate its effectiveness need to be done before gene therapy can be put to regular medical use.

To get a new gene into a cell’s genome, it must be carried in a molecule called a vector. The most common vectors currently being used are viruses, which naturally invade cells and insert their genetic material into that cell’s genome. To use a virus as a vector, the virus’ own genes are removed and replaced with the new gene destined for the cell. When the virus attacks the cell, it will insert the genetic material it carries. A successful transfer will result in the target cell now carrying the new gene that will correct the problem caused by the faulty gene.

Viruses that can be used as vectors include retroviruses like HIV, adenoviruses (one of which causes the common cold), adeno-associated viruses and herpes simplex viruses. There are also many non-viral vectors being tested for gene therapy uses. These include artificial lipid spheres called liposomes, DNA attached to a molecule that will bind to a receptor on the target cell, artificial chromosomes and naked DNA that is not attached to another molecule at all and can be directly inserted into the cell.

The actual transfer of the new gene into the target cell can happen in two ways: ex vivo and in vivo. The ex vivo approach involves transferring the new gene into cells that have been removed from the patient and grown in the laboratory. Once the transfer is complete, the cells are returned to the patient, where they will continue to grow and produce the new gene product. The in vivo approach delivers the vector directly to the patient, where transfer of the new gene will occur in the target cells within the body.

Conditions or disorders that result from mutations in a single gene are potentially the best candidates for gene therapy. However, the many challenges met by researchers working on gene therapy mean that its application is still limited while the procedure is being perfected.

Before gene therapy can be used to treat a certain genetic condition or disorder, certain requirements need to be met:

Clinical trials for gene therapy in other countries (for example France and the United Kingdom) have shown that there are still several major factors preventing gene therapy from becoming a routine way to treat genetic conditions and disorders. While the transfer of the new gene into the target cells has worked, it does not seem to have a long-lasting effect. This suggests that patients would have to be treated multiple times to control the condition or disorder. There is also always a risk of a severe immune response, since the immune cells are trained to attack any foreign molecule in the body. Working with viral vectors has proven to be challenging because they are difficult to control and the body immediately recognizes and attacks common viruses. Recent work has focussed on potential non-viral vectors to avoid the complications associated with the viral vectors. Finally, while there are thousands of single-gene disorders, the more common genetic disorders are actually caused by multiple genes, which do not make them good candidates for gene therapy.

One promising application of gene therapy is in treating type I diabetes. Researchers in the United States used an adenovirus as a vector to deliver the gene for hepatocyte growth factor (HGF) to pancreatic islet cells removed from rats. They injected the altered cells into diabetic rats and, within a day, the rats were controlling their blood glucose levels better than the control rats. This model mimics the transplantation of islet cells in humans and shows that the addition of the HGF gene greatly enhances the islet cells’ function and survival.

In Canada, researchers in Edmonton, Alberta also developed a protocol to treat type I diabetes. Doctors use ultrasound to guide a small catheter through the upper abdomen and into the liver. Pancreatic islet cells are then injected through the catheter into the liver. In time, islets are established in the liver and begin releasing insulin.

Another application for gene therapy is in treating X-linked severe combined immunodeficiency (X-SCID), a disease where a baby lacks both T and B cells of the immune system and is vulnerable to infections. The current treatment is bone marrow transplant from a matched sibling, which is not always possible or effective in the long term. Researchers in France and the United Kingdom, knowing the disease was caused by a faulty gene on the X chromosome, treated 14 children by replacing the faulty gene ex vivo. Upon receiving the altered cells, the patients showed great improvements in their immune system functions. Unfortunately, two of the children developed a form of leukemia several years after the treatment. Further investigation showed that the vector had inserted the gene near a proto-oncogene, which led to uncontrolled growth of the T cells. The clinical trials were put on hold until a safer method can be designed and tested.

Link:

Gene Therapy – Biotechnology – Science and Research

Home – Weatherall Institute of Molecular Medicine

The mission of the MRC Weatherall Institute of Molecular Medicine (WIMM) is to undertake internationally competitive research into the processes underlying normal cell and molecular biology and to determine the mechanisms by which these processes are perturbed in inherited and acquired human diseases. It is also our mission to translate this research to improve human health. The WIMM is uniquely placed among biomedical institutes throughout the world in its pioneering vision of combining outstanding clinical research with excellent basic science. The WIMM Faculty currently includes an equal mixture of scientists and clinicians working together and in collaboration with the National Institute of Health Research, the NHS and commercial companies with the aim of improving the diagnosis and treatment of human diseases. The major topics of current research include haematology, immunology, stem cell biology, oncology and inherited human genetic diseases. The Institute benefits from strategic support from the MRC.

The Institute values communication with members of the broader scientific community and the general public and with the support of the Medical Research Council (MRC) we have commissioned three short videos to explain our mission.

Professor Jan Rehwinkels team from the MRC Human Immunology Unit have found that human cells use viruses as Trojan horses, transporting a messenger that encourages the immune system to fight the very virus that carries it. The discovery could have implications for the design of new vaccines. Scientists already knew that when a virus containing or producing DNA enters a cell in the body it is detected by a protein called cGAS. This in turn …

Every year in early summer, a team of dedicated volunteers at the WIMM put together a series of fund-raising activities in aid of a local charity, which is often chosen because the beneficiary has links to staff and students at the Institute. This year, the WIMM decided to support UCARE (Urology Cancer Research and Education), a charity based at the nearby Churchill Hospital in Oxford which aims to improve the treatment and care of patients …

News Archive

Applications are invited for an enthusiastic Statistical Bioinformatician/Geneticist to join an existing research team (Clinical Genetics Group) led by Professor Andrew Wilkie FRS at the Weatherall Institute of Molecular Medicine (WIMM). This is a fixed-term position funded until 31 January 2019 by the Wellcome Trust, available immediately. This position will allow the successful candidate to participate in several focused research projects and …

Further Vacancies

Vitamins help your immune system fight infection but not how you might think!

We all know that its important to eat our greens, but can any of us actually explain why? Vitamins are critical for the normal growth and function of our bodies, but not always in entirely expected ways. In this latest blog, Lauren Howson explains how a subset of white blood cells can use vitamins to detect and fight bacterial infections. Who knew?

WIMM Blog Archive

Originally posted here:

Home – Weatherall Institute of Molecular Medicine

Are Psoriasis and Allergies Linked?

If you have psoriasis and allergies, maybe you’ve wondered if your allergy flares make your skin condition worse.

There’s no need to guess: Doctors and researchers haven’t found links between the two problems. Here, four experts break down both conditions and explain what can trigger them.

Although psoriasis and allergies both involve your immune system, the causes for them aren’t related.

Psoriasis is an autoimmune disease. That means your body’s immune system wrongly attacks some of its own healthy cells.

An allergy happens when your immune system has a severe reaction to something that most people don’t have a problem with, like pollen, pet dander, or certain foods.

Some people confuse psoriasis for allergies before they visit the doctor, because both conditions can cause itchy, red skin.

A lot of people come in thinking they have allergic skin problems and when I see them, they’ve got psoriasis, says Clifford Bassett, MD, an allergist and immunologist in New York City. “If you suspect it’s one thing, it could be something else.

So, get checked by a dermatologist if your skin itches or flakes, he says.

If you have psoriasis, stress may be partly to blame when the disease first appears and when it flares. Stress can also make your allergies act up.

When you’re having an allergic reaction, your body is working hard, says Julie Pena, MD, a dermatologist in private practice in Nashville. It’s trying to fight something. When your body is going through stressful events, it alters the immune system. We know that stress can cause psoriasis to flare, [even] the internal stress of what your body is going through.

See more here:

Are Psoriasis and Allergies Linked?

New potential for personalized treatments in bowel cancer

Scientists have found that genetic changes in bowel tumours are linked to the way the body’s immune system responds to the cancer, according to research published today (Monday) in the journal Oncoimmunology*.

For the first time, Cancer Research UK researchers at the University of Birmingham have found that certain genetic flaws in bowel cancer are more likely to trigger an immune response at the site of tumours, meaning that treatments to boost this immune response further could potentially be helpful for these patients.

Finding out what’s happening in a cancer patient’s immune system can be difficult and takes time. These findings suggest that genetic profiles of patients’ tumours could be used as an easy and fast way of diagnosing whether they are suitable for immunotherapy treatments, and if so which ones.

Cancer Research UK’s FOCUS4** trial is already using the genetics of bowel cancer to offer patients stratified medicine and this study suggests that we could further expand this work to include immunotherapies.

Gary Middleton, Professor of Medical Oncology at the School of Cancer Sciences at the University of Birmingham, said: “The field of immunotherapy is gaining lots of momentum and this study shows a new finding for bowel cancer. We are already using genetic profiling for stratified medicine in bowel cancer in the FOCUS4 trial. But this research indicates that we could marry immunotherapy with the work we are already doing to personalise treatment even more.”

Researchers used The Cancer Genomic Atlas, a large database, to study this relationship. From this research, scientists can now start looking at what causes a weak immune response and in the future, could target drugs to switch off the immune suppression associated with certain genetic mutations.

Nell Barrie, senior science communication manager at Cancer Research UK, said: “This study shows a strong association between certain genetic profiles and immune responses, but we don’t yet fully understand this link. Further research to investigate the fundamentals behind different immune responses could open new doors in drug development.”

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For media enquiries contact Stephanie in the Cancer Research UK press office on 020 3469 5314 or, out of hours, on 07050 264 059.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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New potential for personalized treatments in bowel cancer

Genetic flaws in bowel cancer may trigger immune response at site of tumours

Published on March 23, 2015 at 8:16 AM

Scientists have found that genetic changes in bowel tumours are linked to the way the body’s immune system responds to the cancer, according to research published today (Monday) in the journal Oncoimmunology*.

For the first time, Cancer Research UK researchers at the University of Birmingham have found that certain genetic flaws in bowel cancer are more likely to trigger an immune response at the site of tumours, meaning that treatments to boost this immune response further could potentially be helpful for these patients.

Finding out what’s happening in a cancer patient’s immune system can be difficult and takes time. These findings suggest that genetic profiles of patients’ tumours could be used as an easy and fast way of diagnosing whether they are suitable for immunotherapy treatments, and if so which ones.

Cancer Research UK’s FOCUS4** trial is already using the genetics of bowel cancer to offer patients stratified medicine and this study suggests that we could further expand this work to include immunotherapies.

Gary Middleton, Professor of Medical Oncology at the School of Cancer Sciences at the University of Birmingham, said: “The field of immunotherapy is gaining lots of momentum and this study shows a new finding for bowel cancer. We are already using genetic profiling for stratified medicine in bowel cancer in the FOCUS4 trial. But this research indicates that we could marry immunotherapy with the work we are already doing to personalise treatment even more.”

Researchers used The Cancer Genomic Atlas, a large database, to study this relationship. From this research, scientists can now start looking at what causes a weak immune response and in the future, could target drugs to switch off the immune suppression associated with certain genetic mutations.

Nell Barrie, senior science communication manager at Cancer Research UK, said: “This study shows a strong association between certain genetic profiles and immune responses, but we don’t yet fully understand this link. Further research to investigate the fundamentals behind different immune responses could open new doors in drug development.”

Read this article:

Genetic flaws in bowel cancer may trigger immune response at site of tumours

Researchers in Berlin tweak the immune system to target cells bearing tumor antigens

Researchers at the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch and Charit – Universittsmedizin Berlin, Campus Berlin-Buch, have succeeded in generating cells of the immune system to specifically target and destroy cancer cells. The research findings of Matthias Obenaus, Professor Thomas Blankenstein (MDC and Charit), Dr. Matthias Leisegang (MDC) and Professor Wolfgang Uckert (Humboldt-Universitt zu Berlin and MDC) as well as Professor Dolores Schendel (Medigene AG, Planegg/Martinsried) have now been published in Nature Biotechnology online (doi:10.1038/nbt.3147)*.

The immune system of the body is trained to distinguish between “foreign” and “self” and to recognize and destroy exogenous structures. In cancer, however, the immune system appears to be quite docile in its response. While it is capable of detecting cancer cells because they often bear characteristics (antigens) on their surfaces that identify them as pathologically altered cells, usually the immune system does not mount an attack but rather tolerates them. The reason: The cancer cells are endogenous to the body, and immune cells do not recognize them as foreign, as they would pathogens. The researchers want to break this tolerance in order to develop therapies against cancer.

T cells are the linchpin in the attack of the immune system. On their surface they have anchor molecules (receptors) with which they recognize foreign structures, the antigens of bacteria or viruses, and thus can target and destroy invaders. Cancer researchers and immunologists are attempting to mobilize this property of the T cells in the fight against cancer. The objective is to develop T cells that specifically recognize and attack only cancer cells but spare other body cells.

Now Matthias Obenaus, Professor Blankenstein, Dr. Leisegang, Professor Uckert and Professor Schendel have developed human T cell receptors (TCRs) that have no tolerance toward human cancer antigens and specifically recognize the antigen MAGE-A1, which is present on various human tumor cells. Instead of directly using human-derived TCRs, which do not mediate substantial anti-tumor effects, the scientists took a “detour” over a mouse model.

First, the researchers transferred the genetic information for human TCRs into the mice, thus creating an entire arsenal of human TCRs (Nature Medicine, doi: 10.1038/nm.2197). When the humanized mouse T cells come into contact with human cancer cells, they perceive the tumor antigens as foreign – like viral or bacterial antigens. Thus, the T cells can specifically target, attack and destroy the tumor cells.

The researchers subsequently isolated the human T-cell receptors of these mice, which are specifically targeted toward the tumor antigen MAGE-A1. Then they transferred the T-cell receptors into human T cells, thereby training them to recognize the cancer cells as foreign.

Some people possess T cells which naturally recognize MAGE-A1 on tumor cells, but only in the Petri dish. In studies using an animal model, only the human TCRs derived from mice were shown to be effective against the tumor. The TCRs from human T cells ignored the tumor completely. The comparison with the tweaked human TCRs from the mouse model shows that the TCRs of patients cannot recognize the tumor antigens sufficiently; they are too weak. “The fact that our TCRs from the mouse are better is a strong indication that the T cells of a human are tolerant toward MAGE-A1,” said Matthias Obenaus and Professor Blankenstein.

Using the T-cell receptors they developed, the researchers are planning an initial clinical trial with patients with MAGE-A1 positive multiple myeloma, a malignant disease of the bone marrow.

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*Identification of human T-cell receptors with optimal affinity to cancer antigens using antigen-negative humanized mice Matthias Obenaus1, Catarina Leito1,7, Matthias Leisegang1, Xiaojing Chen1, Ioannis Gavvovidis1 Pierre van der Bruggen2,3, Wolfgang Uckert1,4, Dolores J Schendel5 & Thomas Blankenstein1,6 1Max Delbrck Center for Molecular Medicine, Berlin, Germany. 2Ludwig Institute for Cancer Research, Brussels, Belgium. 3De Duve Institute, Universit Catholique de Louvain, Brussels, Belgium. 4Institute of Biology, Humboldt University, Berlin, Germany. 5Medigene AG, Planegg/Martinsried, Germany. 6Institute of Immunology, Charit Campus Buch, Berlin, Germany. 7Present address: Institute for Molecular and Cell Biology, Porto, Portugal.

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Researchers in Berlin tweak the immune system to target cells bearing tumor antigens

With genetic engineering, scientists use decoy molecule to trick HIV

An effective vaccine for HIV has eluded researchers for several decades, due to the pathogen’s infamous shape-shifting abilities.

Even though researchers have identified certain broadly neutralizing antibodies that can conquer multiple strains of the human immunodeficiency virus, many strains of rapidly mutating HIV remain resistant to the these super antibodies.

In recent years however,researches have proposed a new method of battling the virus that involves gene therapy.

Instead of using a vaccine to stimulate the body’s own immune system, so that it produces HIV antibodies, scientists are bypassing the immune system entirely.

In experiments involving rats and monkeys, the researchers have used non-life-threatening viruses to alter the animals’ genome so that its cells produce designer molecules capable of neutralizing HIV.

In a paper published Wednesday in the journal Nature, a team of researchers said they had used the technique to protect rhesus macaques from repeated intravenous injections of a SHIV, a combination of simian immunodeficiency virus and humanimmunodeficiency virus.

The technique, researchers said, “can function like an effective HIV-1 vaccine.” (HIV-1 is the main family of the virus, and accounts for most infections worldwide.)

When HIV enters the body, it attacks specific immune cells. As the virus copies itself over and over, and kills more and more host cells, the immune system grows progressively weaker. If left untreated, this progressive weakening will give rise to AIDS.

In most cases, the HIV virus begins its attack by latching onto two separate protein structures on the surface of its target white blood cells. One of these structures is called CD4, and the other is called CCR5.

In the Nature study, researchers set out to engineer an antibody-like molecule that would mimic both of these proteins, so that it would act as decoy of sorts for the virus. Instead of latching onto a host cell, HIV would latch onto a specially enhanced protein molecule, or eCD4-Ig, that was released by the cell.

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With genetic engineering, scientists use decoy molecule to trick HIV

A new twist on HIV vaccines shows results in monkeys, study says

An effective vaccine for HIV has eluded researchers for several decades, due to the pathogen’s infamous shape-shifting abilities.

Even though researchers have identified certain broadly neutralizing antibodies that can conquer multiple strains of the human immunodeficiency virus, many strains of rapidly mutating HIV remain resistant to the these super antibodies.

In recent years however,researches have proposed a new method of battling the virus that involves gene therapy.

Instead of using a vaccine to stimulate the body’s own immune system, so that it produces HIV antibodies, scientists are bypassing the immune system entirely.

In experiments involving rats and monkeys, the researchers have used non-life-threatening viruses to alter the animals’ genome so that its cells produce designer molecules capable of neutralizing HIV.

In a paper published Wednesday in the journal Nature, a team of researchers said they had used the technique to protect rhesus macaques from repeated intravenous injections of a SHIV, a combination of simian immunodeficiency virus and humanimmunodeficiency virus.

The technique, researchers said, “can function like an effective HIV-1 vaccine.” (HIV-1 is the main family of the virus, and accounts for most infections worldwide.)

When HIV enters the body, it attacks specific immune cells. As the virus copies itself over and over, and kills more and more host cells, the immune system grows progressively weaker. If left untreated, this progressive weakening will give rise to AIDS.

In most cases, the HIV virus begins its attack by latching onto two separate protein structures on the surface of its target white blood cells. One of these structures is called CD4, and the other is called CCR5.

In the Nature study, researchers set out to engineer an antibody-like molecule that would mimic both of these proteins, so that it would act as decoy of sorts for the virus. Instead of latching onto a host cell, HIV would latch onto a specially enhanced protein molecule, or eCD4-Ig, that was released by the cell.

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A new twist on HIV vaccines shows results in monkeys, study says

'Miracle' stem cell therapy reverses multiple sclerosis

In the new treatment, specialists use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patients own blood.

Stem cells are so effective because they can become any cell in the body based on their environment.

“Since we started treating patients three years ago, some of the results we have seen have been miraculous,” Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, told The Sunday Times.

“This is not a word I would use lightly, but we have seen profound neurological improvements.”

During the treatment, the patient’s stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.

The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.

Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.

Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two.

But she claims the new treatment has transformed her life.

It worked wonders, she said. I remember being in the hospital… after three weeks, I called my mum and said: ‘I can stand’. We were all crying.

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'Miracle' stem cell therapy reverses multiple sclerosis

Vault Nano Inc. Announces Granting of U.S. Cancer Immune Therapy Patent Supporting ImmunOncologyTM Programs and …

(PRWEB) February 06, 2015

Los Angeles, California: Vault Nano Inc. (VNI), a biotechnology company developing vault medicines, was granted U.S. patent Vault Complexes for Cytokine Delivery. This patent is part of a multi-patent family protecting VNIs cytokine-based immune therapy strategy for treating cancer. Discovered by the Rome Laboratory at UCLA, the ImmunOncologyTM portfolio is based on a novel human protein nanoparticle, called a vault. VNIs therapies are poised to make a clinical impact in multiple metastatic cancers.

The patent is part of an extensive intellectual property portfolio licensed from the University of California Los Angeles and developed by Vault Nano. UCLA is a terrific partner for Vault Nano, said Oliver Foellmer, VNIs Chief Operating Officer. Our ongoing development of the vault technology is strongly supported by strategic collaborations of Vault Nano with multiple laboratories at the university.

Vault Nano is focused on changing the treatment paradigm in cancer. VNIs ImmunOncologyTM portfolio is based on the unique ability of vault particles to present active payloads to the immune system. This effect enhances the action of our active ingredient to recruit and educate immune cells to the tumor, said Professor Leonard Rome. Vaults really are a unique nanoparticle in that they are inherently a human particle that remains bio-invisible while delivering therapeutic messages to the immune system. Our therapeutic, VNI-101, rallies the patients own defenses against the tumor anywhere in the body. VNI-101 is currently being prepared for clinical testing against late stage lung cancer at UCLAs Jonsson Comprehensive Cancer Center (JCCC) and for the initiation of human clinical safety testing by the end of 2015.

VNI-101 will initially be tested in patients with stage IV non small cell lung carcinoma and will ultimately be applied to melanoma and other metastatic cancers. The drug will be the cornerstone of multiple anti-cancer immune therapies being developed by the company that promise to be highly effective, while simultaneously reducing the long-term toxicity associated with todays chemotherapeutics. VNI-101 is part of a pharmaceutical industry movement of immune modulating drugs making their way toward the cancer market. Immune Oncology is a hot area today and will grow significantly in the coming years, said Michael Laznicka, VNI Chairman and CEO. The most exciting aspect of our ImmunOncologyTM approach is that it is highly synergistic with pharmaceutical checkpoint inhibitor programs. We envision that by combining our vault medicines with other immune therapy approaches we will be able to lower dose-dependent side effects and enhance effectiveness to the point where a discussion of short-term survival can transition to one of curative long-term health.

About Vault Nano Inc. Vault Nano Inc., located in Los Angeles, California, is the leading biotechnology company in developing and commercializing Vault Medicines. VNIs mission is to develop safe and effective immunotherapeutics with the goal of changing the existing treatment paradigm of life-threatening and debilitating diseases.

Activating the Immune System to Destroy Cancer Immune Medicine Powered by Vaults

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Vault Nano Inc. Announces Granting of U.S. Cancer Immune Therapy Patent Supporting ImmunOncologyTM Programs and …

Space flight can age immune system prematurely

Spending long duration on space flights may accelerate ageing of the immune system in astronauts, finds a research.

“This study shows that a model of spaceflight conditions could not only be used to test the efficacy of molecules to improve immune responses following a spaceflight in astronauts but also in the elderly and bed-ridden populations on Earth,” said Jean-Pol Frippiat, researcher from Lorraine University in Vandoeuvre-les-Nancy, France.

This model could also help understanding the aging of the immune system called immunosenescence, he said.

Frippiat and colleagues used a ground-based model called hindlimb unloading (or HU), that simulates some of the effects of spaceflight on mice.

“Getting to Mars and beyond promises to be a huge task, requiring contributions from almost every scientific discipline,” said Gerald Weissmann, editor-in-chief of The FASEB Journal that published the paper.

“For biologists and medical researchers, knowing how altered gravity affect our immune system from challenges aloft can already be studied on Earth. Fortunately for biologists, it is not rocket science,” he said.

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Space flight can age immune system prematurely

Ottawa patients sought for testing of stem cell therapy …

Retired teacher Margo Murchison does not qualify for the testing of stem cell treatments for MS but she says the possible breakthrough gives her hope.

At a time when there is growing concern about patients travelling overseas for unproven treatments, Canadian doctors are beginning clinical trials of stem cell therapy they say offers real hope for people with multiple sclerosis.

Dr. Mark S. Freedman, director of the multiple sclerosis research unit at The Ottawa Hospital, will lead the Canadian trials which are funded with a $4.2-million grant from the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation.

This is the first major stem cell trial that is going on in MS right now around the world, he said. There is so much noise about stem cells in general and the hype that surrounds them, we are doing this study properly so we can answer the question for once and for all.

Recent publicity around hockey legend Gordie Howes stem cell treatment in Mexico after he had a stroke has focused attention on a growing international stem cell tourism industry offering therapies that have not been approved for use in Canada or the United States.

Freedman said he sees patients who are willing to travel overseas to try risky and expensive treatments out of desperation. He said he worries that foreign clinics are preying on patients desperation by providingtreatment that is not properly tested, is not proven to do any good and could carryserious risks. That is why it is crucialto conductproper clinical trials, said Freedman, who is also a professor at the University of Ottawa.

The potential for stem cell treatment is significant in Canada, which has the highest rates of MS in the world.

The study announced Thursday will involve treating 40 patients 20 in Ottawa and 20 in Winnipeg with mesenchymal stem cells (MSCs), extracted from the patients own bone marrow and then grown in a specialized lab. The cells are later given to the same patient intravenously.

The cells are less risky to use than other stem cell therapies, and their potential seems to come from their ability to modify the immune system, by reducing inflammation, fas well as helping to prevent and repair tissue damage. Patients do not require chemotherapy to kill their immune system as they do with some other treatments.

The Canadian randomized control trials join others underway around the world. In total, 200 patients in nine countries will be part of the trial that could result in routine clinical treatment for MS patients.

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Ottawa patients sought for testing of stem cell therapy …

Early Study Says Stem Cells May Reverse Multiple Sclerosis Disability

By Amy Norton HealthDay Reporter

TUESDAY, Jan. 20, 2015 (HealthDay News) — A therapy that uses patients’ own primitive blood cells may be able to reverse some of the effects of multiple sclerosis, a preliminary study suggests.

The findings, published Tuesday in the Journal of the American Medical Association, had experts cautiously optimistic.

But they also stressed that the study was small — with around 150 patients — and the benefits were limited to people who were in the earlier courses of multiple sclerosis (MS).

“This is certainly a positive development,” said Bruce Bebo, the executive vice president of research for the National Multiple Sclerosis Society.

There are numerous so-called “disease-modifying” drugs available to treat MS — a disease in which the immune system mistakenly attacks the protective sheath (called myelin) around fibers in the brain and spine, according to the society. Depending on where the damage is, symptoms include muscle weakness, numbness, vision problems and difficulty with balance and coordination.

But while those drugs can slow the progression of MS, they can’t reverse disability, said Dr. Richard Burt, the lead researcher on the new study and chief of immunotherapy and autoimmune diseases at Northwestern University’s Feinberg School of Medicine in Chicago.

His team tested a new approach: essentially, “rebooting” the immune system with patients’ own blood-forming stem cells — primitive cells that mature into immune-system fighters.

The researchers removed and stored stem cells from MS patients’ blood, then used relatively low-dose chemotherapy drugs to — as Burt described it — “turn down” the patients’ immune-system activity.

From there, the stem cells were infused back into patients’ blood.

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Early Study Says Stem Cells May Reverse Multiple Sclerosis Disability

New Cellular Pathway Triggering Allergic Asthma Response Identified

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Newswise Researchers at the University of California, San Diego School of Medicine, with collaborators in Korea and Scotland, have identified a novel signaling pathway critical to the immune response of cells associated with the initiation of allergic asthma. The discovery, they say, could point the way to new therapies that suppress the inflammatory allergic response, offering potential relief to millions of Americans with the chronic lung condition and potentially other allergic diseases.

The results are published in the January 19 online Early Edition of the Proceedings of the National Academy of Sciences.

Specifically, the scientists demonstrated that T helper 2 (Th2) type inflammation in allergic asthma involves dendritic cells (DC), a type of white blood cell, which trigger a reduction in the production of cyclic AMP or cAMP, a key messenger molecule for signaling inside cells. In mouse models, deletion of the gene that codes for a protein that promotes the production of cAMP resulted in spontaneous bronchial asthma, which shares many similarities with human asthma. Conversely, increasing cAMP levels inhibited the cells inflammatory response that results in asthmas characteristic symptoms.

These findings and the related mechanism are very different from the current residing view of activation of specific T helper cell responses, said principal investigator Eyal Raz, MD, professor of medicine.

The role of cAMP formation and action in dendritic cells in the induction of allergic response was really surprising, added co-author Paul Insel, MD, professor of pharmacology and medicine. It suggested to us that this signaling pathway is involved in other immune-related functions.

The immune response of humans, mice and other vertebrates consists of two fundamental components. The first is the innate immune system, which recognizes and responds to pathogens in an immediate, but generalized, way and does not confer long-lasting immunity. The second is the adaptive immune system in which highly specialized T and B cells eliminate or prevent pathogen growth and create immunological memory in case of future encounters with the same pathogen.

Th2 immunity is one of two major aspects of adaptive immunity. Th1 responses target intracellular pathogens, such as viruses and bacteria that have invaded host cells. The Th2 response is more effective against extracellular pathogens (such as bacteria, parasites and toxins that operate outside of cells) and also plays a major role in allergic reactions and related diseases.

Allergic asthma is triggered by inhaled allergens, such as pet dander, pollen, mold and dust mites. It is characterized by inflammation and narrowing of the airways, resulting in wheezing, chest tightness, shortness of breath, coughing and other symptoms. The common form of allergic asthma is associated with an exaggerated Th2 immune response. Allergic asthma affects people of all ages, most often appearing in childhood. More than 25 million Americans suffer from the condition.

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New Cellular Pathway Triggering Allergic Asthma Response Identified

UMMS to develop a model for predicting gene expression in dendritic cells

Insight into regulation of the genes that allow the immune system to recognize pathogens will help scientists rationally design new vaccines and prevent autoimmunity

WORCESTER, MA – UMass Medical School scientists Jeremy Luban, MD, and Manuel Garber, PhD, will be principal investigators on a 3-year, $6.1 million grant to develop a model for predicting whether a given gene will be turned on or off under specific conditions. Funding for the grant comes from the recently launched Genomics of Gene Regulation (GGR) program at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health. In total, $28 million in new grants aimed at deciphering the language of gene expression were awarded.

“Why a certain gene is expressed in a specific cell at a given time is an essential biological question that is fundamental to our understanding of life and disease,” said Dr. Luban, MD, the David J. Freelander Professor in AIDS Research and professor of molecular medicine. “This grant will help us decipher the rules that govern gene expression. Ultimately, such information will help explain why one person survives a viral infection and another person does not.”

Dr. Garber, PhD, director of the Bioinformatics Core and associate professor of molecular medicine said “Understanding of the regulatory code network – the DNA elements that control when and for how long a gene is expressed – has been elusive. The work we’ll carry out in this project will allow us to model and test the regulatory code of dendritic cells. As a result, we would be able to predict the impact of mutations that do not directly affect the gene product but that affect how and when the gene is made.”

Over the past decade, new scientific evidence suggests that genomic regions outside of the primary protein-coding regions of our DNA harbor variations that play an important role in disease. These regions contain elements that control gene expression and, when altered, can increase the risk for a disease.

The GGR grants will allow researchers to study complex gene networks and pathways in different cells types and systems. The resulting insight into the mechanisms controlling gene expression may ultimately lead to new avenues for developing treatments for diseases affected by faulty gene regulation, such as cancer, diabetes and Parkinson’s disease.

“There is a growing realization that the ways genes are regulated to work together can be important for understanding disease,” said Mike Pazin, PhD, a program director in the Functional Analysis Program in NHGRI’s Division of Genome Sciences. “The Genomics of Gene Regulation program aims to develop new ways for understanding how the genes and switches in the genome fit together as networks. Such knowledge is important for defining the role of genomic differences in human health and disease.”

Luban and Garber will be working with UMMS colleagues Job Dekker, PhD, co-director of the Program in Systems Biology and professor of biochemistry & molecular pharmacology; Oliver Rando, PhD, MD, professor of biochemistry & molecular pharmacology, and Scot Wolfe, associate professor of biochemistry & molecular pharmacology, to develop a model system for exploring gene regulation using human dendritic cells.

The dendritic cell is a key part of the innate immune system that distinguishes self from non-self and, when appropriate, directs the body to attack invading pathogens. In its immature state dendritic cells help prevent autoimmunity by keeping the immune system’s T-cells from attacking the body’s own cells. When an immature dendritic cell encounters a pathogen, though, a developmental switch is activated and the cell undergoes profound changes in gene expression as it matures. In contrast to immature dendritic cells, these mature cells elicit a potent immune response from T-cells that targets the pathogen.

Luban, Garber and colleagues will examine the changes that the dendritic cell undergoes when it encounters a pathogen and moves from the immature to the mature state. Among the factors they will look at are the genes that are turned on and off during this process. They will examine changes in transcription factors, chromatin modifying enzymes and the cis-acting DNA elements. Linking these elements to specific changes in gene expression should provide a model for predicting the expression of specific genes in dendritic and other cells.

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UMMS to develop a model for predicting gene expression in dendritic cells