StemCell Therapy

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Recommendations You can boost your Immunity by: 1) Reversing Damage - Years of stressful living caused damage to your Immune System. To help reverse this, Immunice releases hundreds of phytonutrients that act at the molecular level to enhance T cell activation, improve proliferation of Lymphocytes, bone marrow cells, and Thymocytes, increase antibody, Leucocyte, Cytokine, and red blood cell production, raise mast cell levels, and stimulate Phogocytosis and plasma fibrinolytic activity in your body. 2) Exercising Regularly - Regular exercise elevates the level of leukocytes, an Immune System cell that fights infection. Exercise also increases release of endorphins, natural hormones that heighten your sense of well being and improve sleep quality, both of which have positive effects on your Immune System. Exertion stimulates the cardiovascular system, improves blood flow, circulates antibodies, flushes toxins from muscles and organs, removes germs, and helps keep the kidneys and endocrine system fully functional. Moderate exercise must be repeated on a near-daily basis so that there is a cumulative effect that leads to a long-term immune response. Getting your heart rate up for just 20 minutes three times a week is associated with increased immune function, and a 30-minute brisk walk five days a week can help reduce your risk of catching a cold. Walking strengthens your cardiovascular system and blood flow. Walk ten minutes, three times a day if you are unable to walk 30 ...From:ihholisticsViews:0 0ratingsTime:11:52More inEducation

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A research team at the Yale School of Medicine has found a way to save platelets and white blood cells from the adverse effects of chemotherapy.

Led by School of Medicine genetics professor Jun Lu, the team conducted its research at the Yale Stem Cell Center over the past three years. By manipulating a microRNA molecule called miR-150, researchers were able to increase proliferation of white blood cells and platelets in mice, thus strengthening their immune systems, Lu said.

The human blood system is characterized by a rapid turnover of blood cells and platelets, Lu said. During chemotherapy, these cells have a shorter life span because they are being attacked by the drugs. The human body has not evolved to respond efficiently to chemotherapy, and as a result does not produce enough blood cells and platelets, leading to a compromised immune system.

Typically, miR-150 acts like a brake in a car, preventing white blood cells from overproliferation, said study contributor Prem Reddy of The Scripps Research Institute. The microRNA controls cell production by regulating the activity of the Myb gene, which influences the proliferation of white blood cells and platelets. When uncontrolled, the Myb gene can cause cancer by excessive production of these cells, Reddy said. High miR-150 levels lead to the production of fewer cells, he added.

While normal regulation will not harm people with healthy immune systems, these effects can be damaging to chemotherapy patients.

In a normal adult, approximately 10 billion white blood cells must be generated every day to compensate for daily loss, Lu said. For patients undergoing chemotherapy, which kills both cancerous and noncancerous cells, the necessary rate of generation is even higher. If miR-150 is suppressed and Myb levels are allowed to increase, enough cells can be generated to prevent the immune system from being compromised, Reddy said.

Massachusetts Institute of Technology biology professor Phil Sharp, a 1993 recipient of the Nobel Prize in physiology or medicine, said he considers this research interesting and novel. Although there are growth factor therapies that regenerate a patients immune system, this isolation and targeting of microRNA has not been done in previous studies, he said.

Before the studys findings are applied in a patient setting, however, Lus team will have to replicate these results in humans. They will then have to find or create drugs that will help suppress miR-150 and determine ways to deliver these drugs to cells of interest in the body, Lu said. After these steps, they will be able to conduct clinical trials.

If the drug the team finds is already approved by the United States Food and Drug Administration, Lu said, the clinical trial phase may be shorter, as its side effects will already be known.

Sharp said that while it may take years before this technique is used in humans, Lus findings show promise.

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Technique shields immune system from chemo effects

* Vaccine was safe, showed signs of being effective

* Vaccine aims to train immune system to fight cancer

By Julie Steenhuysen

CHICAGO, Oct (KOSDAQ: 039200.KQ - news) 10 (Reuters) - A new type of cervical cancer vaccine made by Inovio Pharmaceuticals (AMEX: INO - news) has shown early promise as a potential treatment for pre-cancerous changes in the cervix, researchers at the company said on Wednesday.

Instead of preventing infections caused by certain strains of the human papillomavirus or HPV, as is the aim of Merck (BSE: MERCK.BO - news) 's Gardasil and GlaxoSmithKline (Other OTC: GLAXF.PK - news) 's Cervarix vaccine, the Inovio vaccine is designed to train the immune system to kill cells that spur cancer growth in women who are already infected.

Cervical cancer is the second most common cancer among women globally, causing 493,000 new cases and 274,000 deaths each year. About 10 to 25 percent of women who develop moderate to severe pre-cancerous lesions in their cervix, known as cervical intraepithelial neoplasia, are able to clear them on their own.

"It was not clear why that happens," said Joseph Kim, chief executive of Inovio Pharmaceuticals, which funded the study.

But many of these women tend to have higher levels of immune system cells known as T cells against two HPV-specific, cancer-causing genes known as E6 and E7 oncogenes.

The company set out to develop a vaccine to train a patient's immune system to make large quantities of these cells which could specifically target and kill these oncogenes.

"That is what this study has shown," Kim said of research published in the journal Science Translational Medicine.

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Vaccine to treat cervical cancer shows early promise

Public release date: 1-Oct-2012 [ | E-mail | Share ]

Contact: John Wallace wallacej@vcu.edu 804-628-1550 Virginia Commonwealth University

Richmond, Va. (October 1, 2012) A novel therapy in the early stages of development at Virginia Commonwealth University Massey Cancer Center shows promise in providing lasting protection against the progression of multiple myeloma following a stem cell transplant by making the cancer cells easier targets for the immune system.

Outlined in the British Journal of Hematology, the Phase II clinical trial was led by Amir Toor, M.D., hematologist-oncologist in the Bone Marrow Transplant Program and research member of the Developmental Therapeutics program at VCU Massey Cancer Center. The multi-phased therapy first treats patients with a combination of the drugs azacitidine and lenalidomide. Azacitidine forces the cancer cells to express proteins called cancer testis antigens (CTA) that immune system cells called T-cell lymphocytes recognize as foreign. The lenalidomide then boosts the production of T-cell lymphocytes. Using a process called autologous lymphocyte infusion (ALI), the T-cell lymphocytes are then extracted from the patient and given back to them after they undergo a stem cell transplant to restore the stem cells' normal function. Now able to recognize the cancer cells as foreign, the T-cell lymphocytes can potentially protect against a recurrence of multiple myeloma following the stem cell transplant.

"Every cell in the body expresses proteins on their surface that immune system cells scan like a barcode in order to determine whether the cells are normal or if they are foreign. Because multiple myeloma cells are spawned from bone marrow, immune system cells cannot distinguish them from normal healthy cells," says Toor. "Azacitidine essentially changes the barcode on the multiple myeloma cells, causing the immune system cells to attack them," says Toor.

The goal of the trial was to determine whether it was safe, and even possible, to administer the two drugs in combination with an ALI. In total, 14 patients successfully completed the investigational drug therapy. Thirteen of the participants successfully completed the investigational therapy and underwent a stem cell transplant. Four patients had a complete response, meaning no trace of multiple myeloma was detected, and five patients had a very good partial response in which the level of abnormal proteins in their blood decreased by 90 percent.

In order to determine whether the azacitidine caused an increased expression of CTA in the multiple myeloma cells, Toor collaborated with Masoud Manjili, D.V.M., Ph.D., assistant professor of microbiology and immunology at VCU Massey, to conduct laboratory analyses on bone marrow biopsies taken from trial participants before and after treatments. Each patient tested showed an over-expression of multiple CTA, indicating the treatment was successful at forcing the cancer cells to produce these "targets" for the immune system.

"We designed this therapy in a way that could be replicated, fairly inexpensively, at any facility equipped to perform a stem cell transplant," says Toor. "We plan to continue to explore the possibilities of immunotherapies in multiple myeloma patients in search for more effective therapies for this very hard-to-treat disease."

In addition to Manjili, Toor collaborated with John McCarty, M.D., director of the Bone Marrow Transplant Program at VCU Massey, and Harold Chung, M.D., William Clark, M.D., Catherine Roberts, Ph.D., and Allison Hazlett, also all from Massey's Bone Marrow Transplant Program; Kyle Payne, Maciej Kmieciak, Ph.D., from Massey and the Department of Microbiology and Immunology at VCU School of Medicine; Roy Sabo, Ph.D., from VCU Department of Biostatistics and the Developmental Therapeutics program at Massey; and David Williams, M.D., Ph.D., from the Department of Pathology at VCU School of Medicine, co-director of the Tissue and Data Acquisition and Analysis Core and research member of the Developmental Therapeutics program at Massey.

###

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Researchers harness the immune system to improve stem cell transplant outcomes

ScienceDaily (Oct. 1, 2012) A novel therapy in the early stages of development at Virginia Commonwealth University Massey Cancer Center shows promise in providing lasting protection against the progression of multiple myeloma following a stem cell transplant by making the cancer cells easier targets for the immune system.

Outlined in the British Journal of Hematology, the Phase II clinical trial was led by Amir Toor, M.D., hematologist-oncologist in the Bone Marrow Transplant Program and research member of the Developmental Therapeutics program at VCU Massey Cancer Center. The multi-phased therapy first treats patients with a combination of the drugs azacitidine and lenalidomide. Azacitidine forces the cancer cells to express proteins called cancer testis antigens (CTA) that immune system cells called T-cell lymphocytes recognize as foreign. The lenalidomide then boosts the production of T-cell lymphocytes. Using a process called autologous lymphocyte infusion (ALI), the T-cell lymphocytes are then extracted from the patient and given back to them after they undergo a stem cell transplant to restore the stem cells' normal function. Now able to recognize the cancer cells as foreign, the T-cell lymphocytes can potentially protect against a recurrence of multiple myeloma following the stem cell transplant.

"Every cell in the body expresses proteins on their surface that immune system cells scan like a barcode in order to determine whether the cells are normal or if they are foreign. Because multiple myeloma cells are spawned from bone marrow, immune system cells cannot distinguish them from normal healthy cells," says Toor. "Azacitidine essentially changes the barcode on the multiple myeloma cells, causing the immune system cells to attack them," says Toor.

The goal of the trial was to determine whether it was safe, and even possible, to administer the two drugs in combination with an ALI. In total, 14 patients successfully completed the investigational drug therapy. Thirteen of the participants successfully completed the investigational therapy and underwent a stem cell transplant. Four patients had a complete response, meaning no trace of multiple myeloma was detected, and five patients had a very good partial response in which the level of abnormal proteins in their blood decreased by 90 percent.

In order to determine whether the azacitidine caused an increased expression of CTA in the multiple myeloma cells, Toor collaborated with Masoud Manjili, D.V.M., Ph.D., assistant professor of microbiology and immunology at VCU Massey, to conduct laboratory analyses on bone marrow biopsies taken from trial participants before and after treatments. Each patient tested showed an over-expression of multiple CTA, indicating the treatment was successful at forcing the cancer cells to produce these "targets" for the immune system.

"We designed this therapy in a way that could be replicated, fairly inexpensively, at any facility equipped to perform a stem cell transplant," says Toor. "We plan to continue to explore the possibilities of immunotherapies in multiple myeloma patients in search for more effective therapies for this very hard-to-treat disease."

In addition to Manjili, Toor collaborated with John McCarty, M.D., director of the Bone Marrow Transplant Program at VCU Massey, and Harold Chung, M.D., William Clark, M.D., Catherine Roberts, Ph.D., and Allison Hazlett, also all from Massey's Bone Marrow Transplant Program; Kyle Payne, Maciej Kmieciak, Ph.D., from Massey and the Department of Microbiology and Immunology at VCU School of Medicine; Roy Sabo, Ph.D., from VCU Department of Biostatistics and the Developmental Therapeutics program at Massey; and David Williams, M.D., Ph.D., from the Department of Pathology at VCU School of Medicine, co-director of the Tissue and Data Acquisition and Analysis Core and research member of the Developmental Therapeutics program at Massey.

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Immune system harnessed to improve stem cell transplant outcomes

24.09.2012 - (idw) University of Gothenburg

Researchers at the Sahlgrenska Academy, University of Gothenburg, Sweden, have identified a molecule in the immune system that could affect hunger and satiety. The researchers hope that new treatments for obesity will benefit from this finding. Interleukin-6 is a chemical messenger in our immune system that plays an important role in fighting off infection. However, recent research has, surprisingly, shown that it can also trigger weight loss. Researchers at Sahlgrenska Academy, University of Gothenburg, have been investigating and managed to identify the specific types of brain cells that are targeted by the interleukin-6 molecule.

The results show that the cells that are affected by interleukin-6 produce substances that not only affect our sense of hunger and fullness but also control the bodys ability to burn fat. Interleukin-6 increases levels of substances in the brain that trigger weight loss, which could explain why high levels of this molecule lead to weight loss, says doctoral student Erik Schle, who is presenting the results in his thesis.

It is known that our normally low levels of interleukin-6 in the brain increase dramatically during an infection, typically accompanied by reduced hunger and fatigue.

Our previous findings would indicate that interleukin-6 can play a key role in regulating the metabolism of healthy individuals too, says Erik Schle.

Although it is not yet fully understood how interleukin-6 in the brain affects bodyweight, the researchers have concluded that anyone whose brain produces plenty of interleukin-6 could be protected against overweight. The thesis also shows that our gut bacteria indirectly affect the substances in the brain that regulate bodyweight.

This is both surprising and new. It could in the long run lead to people fighting obesity by changing what they eat in line with how it affects the brain, says Erik Schle.

Contact; Erik Schle, Sahlgrenska Academy, University of Gothenburg. + 46 31 786 3681 erik.schele@medic.gu.se function fbs_click() {u=location.href;t=document.title;window.open('http://www.facebook.com/sharer.php?u='+encodeURIComponent(u)+'&t='+encodeURIComponent(t),'sharer','toolbar=0,status=0,width=626,height=436');return false;} html .fb_share_link { padding:2px 0 0 20px; height:16px; background:url(http://www.stemcelltherapy.tv/wp-content/uploads/2012/09/29c1d78260e_icon.gif.gif?6:26981) no-repeat top left; } Share on Facebook

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Immune system molecule affects our weight

Researchers have discovered a cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, according to a release from the University of California, Los Angeles. This finding promises to lead to a more profound understanding of how a healthy immune system is created and as well as how disease can cause poor immune function.

The study's senior author, Dr. Gay Crooks, was quoted as saying, " We felt it was especially important to do these studies using human bone marrow, as most research into the development of the immune system has used mouse bone marrow.The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of post-natal life."

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, cancers of the blood. The findings were published online in the journal Nature Immunology.

"The identification of a progenitor in human bone marrow primed for full lymphoid differentiation will now permit delineation of the molecular regulation of the first stages of lymphoid commitment in human hematopoiesis," the authors wrote. "It will also allow understanding of how these processes are affected during aberrant hematopoiesis in disease states."

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Stem Cells & Immune System: "Missing Link" Found

LOS ANGELES UCLA researchers have discovered a type of cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function.

The research was done using human bone marrow, which contains all the stem cells that produce blood during post-natal life.

"We felt it was especially important to do these studies using human bone marrow, as most research into the development of the immune system has used mouse bone marrow," said the study's senior author, Dr. Gay Crooks, co-director of UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and a co-director of the cancer and stem-cell biology program at UCLA's Jonsson Comprehensive Cancer Center. "The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of post-natal life."

The research team was "intrigued to find this particular bone marrow cell, because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life," said Crooks, a professor of pathology and pediatrics.

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, cancers of the blood.

The findings appeared Sept. 2 in the early online edition of the journal Nature Immunology.

Before this study, researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce cells in intermediate stages of development called progenitors, which make various blood lineages, like red blood cells or platelets.

Crooks was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

"Like the stem cells, the progenitor cells are also very rare, so before we can study them, we needed to find the needle in the haystack," said Lisa Kohn, a member of the UCLA Medical Scientist Training Program and first author of the study.

Previous work had found a fairly mature type of lymphocyte progenitor with a limited ability to differentiate, but the new work describes a more primitive type of progenitor primed to produce the entire immune system, Kohn said.

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'Missing link' ties blood stem cells, immune system

Public release date: 2-Sep-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

UCLA researchers have discovered a type of cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function.

The studies were done using human bone marrow, which contains all the stem cells that produce blood during postnatal life.

"We felt it was especially important to do these studies using human bone marrow as most research into the development of the immune system has used mouse bone marrow," said study senior author Dr. Gay Crooks, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and a co-director of the Cancer and Stem Cell Biology program at UCLA's Jonsson Comprehensive Cancer Center. "The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of postnatal life."

The research team was "intrigued to find this particular bone marrow cell because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life," said Crooks, a professor of pathology and pediatrics.

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, or cancers of the blood.

The study appears Sept. 2 in the early online edition of Nature Immunology.

Before this study, researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce intermediate stages of development called progenitors, which make various blood lineages like red blood cells or platelets. Crooks was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

"Like the stem cells, the progenitor cells are also very rare, so before we can study them we needed to find the needle in the haystack." said Lisa Kohn, a member of the UCLA Medical Scientist Training Program and first author in the paper.

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UCLA researchers discover missing link between stem cells and immune system

ScienceDaily (Aug. 31, 2012) UCLA researchers have discovered a type of cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function.

The studies were done using human bone marrow, which contains all the stem cells that produce blood during postnatal life.

"We felt it was especially important to do these studies using human bone marrow as most research into the development of the immune system has used mouse bone marrow," said study senior author Dr. Gay Crooks, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and a co-director of the Cancer and Stem Cell Biology program at UCLA's Jonsson Comprehensive Cancer Center. "The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of postnatal life."

The research team was "intrigued to find this particular bone marrow cell because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life," said Crooks, a professor of pathology and pediatrics.

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, or cancers of the blood.

The study appears Sept. 2 in the early online edition of Nature Immunology.

Before this study, researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce intermediate stages of development called progenitors, which make various blood lineages like red blood cells or platelets. Crooks was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

"Like the stem cells, the progenitor cells are also very rare, so before we can study them we needed to find the needle in the haystack." said Lisa Kohn, a member of the UCLA Medical Scientist Training Program and first author in the paper.

Previous work had found a fairly mature type of lymphocyte progenitor with a limited ability to differentiate, but the new work describes a more primitive type of progenitor primed to produce the entire immune system, Kohn said

Once the lymphoid primed progenitor had been identified, Crooks and her team studied how gene expression changed during the earliest stages of its production from stem cells.

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'Missing link' between stem cells and the immune system

Newswise UCLA researchers have discovered a type of cell that is the missing link between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function.

The studies were done using human bone marrow, which contains all the stem cells that produce blood during postnatal life.

We felt it was especially important to do these studies using human bone marrow as most research into the development of the immune system has used mouse bone marrow, said study senior author Dr. Gay Crooks, co-director of the Eli and Edythe Broad Center of Regenerative Medicine and a co-director of the Cancer and Stem Cell Biology program at UCLAs Jonsson Comprehensive Cancer Center. The few studies with human tissue have mostly used umbilical cord blood, which does not reflect the immune system of postnatal life.

The research team was intrigued to find this particular bone marrow cell because it opens up a lot of new possibilities in terms of understanding how human immunity is produced from stem cells throughout life, said Crooks, a professor of pathology and pediatrics.

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, or cancers of the blood.

The study appears Sept. 2 in the early online edition of Nature Immunology.

Before this study, researchers had a fairly good idea of how to find and study the blood stem cells of the bone marrow. The stem cells live forever, reproduce themselves and give rise to all the cells of the blood. In the process, the stem cells divide and produce intermediate stages of development called progenitors, which make various blood lineages like red blood cells or platelets. Crooks was most interested in the creation of the progenitors that form the entire immune system, which consists of many different cells called lymphocytes, each with a specialized function to fight infection.

Like the stem cells, the progenitor cells are also very rare, so before we can study them we needed to find the needle in the haystack. said Lisa Kohn, a member of the UCLA Medical Scientist Training Program and first author in the paper.

Previous work had found a fairly mature type of lymphocyte progenitor with a limited ability to differentiate, but the new work describes a more primitive type of progenitor primed to produce the entire immune system, Kohn said

Once the lymphoid primed progenitor had been identified, Crooks and her team studied how gene expression changed during the earliest stages of its production from stem cells.

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UCLA Researchers Discover "Missing Link" Between Stem Cells and the Immune System

Public release date: 3-Aug-2012 [ | E-mail | Share ]

Contact: Elisabeth (Lisa) Lyons elyons@cell.com 617-386-2121 Cell Press

Human HLA genes the genes that allow our immune system to tell the difference between our own cells and foreign invaders are evolving much more rapidly than previously thought, according to an article online on August 3rd in Trends in Genetics. The resulting degree of variation improves our ability to fight off disease, but could also present challenges to current worldwide efforts aimed at identifying potential donors for patients undergoing stem cell transplantation.

"This new work makes clear the daunting and near hopeless challenge of keeping track of the continuous output from the HLA mutational spigot," says first author William Klitz, from the University of California, Berkeley.

HLA proteins sit at the surface of human cells. Every individual has a specific HLA on the surface of their cells and these proteins effectively act as an identification card. Any other cells that have the same HLA on the outside are recognized as 'self'; foreign particles like bacteria or viruses are identified as invaders and the immune system kicks in to remove them. The same system that helps us fight off germs makes organ or stem cell transplantation difficult. Our bodies treat transplanted tissue as foreign and reject it. Unless, however, the patient and the donor share the same HLA genes. As a result, worldwide efforts are underway to identify all possible HLA variants, in the hopes of more effectively matching patients with potential donors.

The difficulty is that within the human population, HLA genes are mutating rapidly and Klitz estimates that more than a million variants exist in the current population. Trying to identify all the variants will be nearly impossible and ultimately pointless, according to Klitz, because of how quickly these genes are evolving. This rapid evolution is a boon in some ways because it means that, at the population level, our immune systems are getting better at fighting off pathogens. For transplant recipients, however, the most likely implication is that the best chance for a match will be found in first-degree relatives rather than in a worldwide search for donors.

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Klitz et al.: "New reservoirs of HLA alleles: Pools of rare variants enhance immune defense"

William Klitz, School of Public Health, University of California, Berkeley, CA, USA Philip Hedrick, School of Life Sciences, Arizona State University, Tempe, AZ, USA Ed Louis, Centre for Genetics and Genomics, University of Nottingham, UK

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Unexpected variation in immune genes poses difficulties for transplantation

WASHINGTON People infected with HIV, the virus that causes AIDS, must take anti-retroviral drugs for the rest of their lives in order to control their disease.

Otherwise, reservoirs of dormant virus hiding within the immune system can become active, and the infection can reemerge. Now, researchers have discovered that a cancer drug can dislodge these latent copies of the AIDS virus. They view the development as a critical step toward curing HIV-infected people.

HIV has evolved a way to survive inside the human body by integrating itself into the genetic architecture of immune-system T-cells, the specialized white blood cells targeted by the AIDS virus. Anti-retroviral drugs can suppress HIV to near undetectable levels, giving the immune system a chance to repair itself. But the AIDS virus is always lurking in miniscule numbers - roughly one in every million T cells - and threatening to come back to life should an individual ever stop taking the anti-retroviral cocktail.

Now, researchers have succeeded in flushing this latent virus out of its hiding place, with a drug used to treat lymphoma, a rare and potentially deadly cancer of the lymphatic system.

David Margolis, a professor of microbiology and immunology at the University of North Carolina Chapel Hill has been studying how HIV hides, dormant, within immune-system cells, says that in some lymphomas, the drug, vorinostat, makes cancer cells die. But Margolis adds that in HIV-infected cells, the cancer drug causes the latent virus to show itself.

Theoretically, doing this clinically would be a way to sort of unmask the hidden virus; flush the virus out of hiding," he says. "And that might then allow us to develop ways to get rid of the leftover virus in people that are on treatment so they could stop treatment and there would be nowhere for the virus to come back from.

Margolis and his colleagues studied eight HIV-infected patients who were medically stable on anti-retroviral therapy. Their levels of HIV CD4 T cells, which the virus uses to reproduce itself, were measured both before and after the men were given vorinostat.

What we saw in every single person was a tiny amount of virus detectable before the dose of the drug," he says. "And the amount of virus that was detectable went up on average about five-fold, five times, after a single exposure to the drug.

Margolis says his so-called proof of concept experiment demonstrates that HIV can be flushed out of hiding with vorinostat and then targeted for destruction by anti-AIDS drugs.

But none of the participants was cured, he adds.

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Cancer Drug Unmasks HIV in Immune Cells

Following the success of antiretroviral therapy for HIV, some researchers are now focusing their attention on a loftier goal a cure. That means targeting viral reservoirs, primarily the long-lived cells of the immune system in which the virus lies dormant. Eliminating these reservoirs isnt easy, but recent research offers glimmers of hope that it may one day be possible.

The strongest proof that HIV can be cured comes from the case of Timothy Brown, who was infected with HIV until he received a stem-cell transplant in 2007 to treat leukaemia1. He has remained free of HIV since then. Browns transplant helped cure his HIV, in part, because the donor's stem cells lacked a key receptor that the virus needs to enter cells.

Particles of HIV that are invisible to the immune system must be flushed out before the disease can be said to be cured.

SCIEPRO/Getty Images

But at this week's XIX International AIDS Conference in Washington DC, Timothy Henrich, an infectious-disease physician at the Brigham and Womens Hospital in Boston, Massachusetts, reported a study of two HIV-infected men who received transplants of stem cells that did have the HIV receptor. Since they received a milder dose of chemotherapy than Brown prior to their transplants, they were able to continue taking antiretrovirals throughout the procedure. The transplants did not immediately eliminate the mens infected immune cells, but roughly ten months later, the men had no evidence of HIV in their blood.

After their transplants, both men developed graft-versus-host disease, in which donor immune cells attack the transplant patients cells. Henrich and his colleagues speculate that the antiretroviral drugs protected the donor cells from infection with HIV. These healthy donor cells then destroyed the HIV-infected cells, leaving the men free of virus.

Theoretically, they could be cured because the immune system was rebuilt under the coverage of antiviral therapy, says Steven Deeks, an HIV researcher at the University of California, San Francisco, who wasnt involved in the research. The ultimate test, however, will be to see whether the men remain HIV-free when they stop taking antiretroviral medicines. Henrich is working with the patients, their physicians and an ethics board to determine whether that is feasible.

But stem cell transplants are too risky to be used on people who dont have a life-threatening illness. This is not scalable or affordable or reasonable or ethical in anyone else, Deeks says.

A more palatable tactic would be to purge the virus from its main hiding spot the long-lived memory cells of the immune system, called CD4+ memory T cells. A paper published this week in Nature provides the first evidence that this may be possible in humans2 (see 'Drug brings HIV out of hiding'). David Margolis, an HIV expert at the University of North Carolinas Center for Infectious Diseases in Chapel Hill, and his colleagues administered a cancer drug called vorinostat (suberoylanilide hydroxamic acid) to eight people in an attempt to coax dormant HIV out of hiding.

A single dose of the medicine produced a 4.8-fold increase in HIV RNA expression. The hope is that this results in HIV particles being made and released, so that they are visible to the patient's immune system again. However, it is still unclear to scientists whether this increased expression will lead to the destruction of HIV-infected cells and shrink the viral reservoir. But it's a positive signal, says Nicolas Chomont, an HIV researcher at the Vaccine & Gene Therapy Institute of Florida in Port St Lucie.

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Dormant HIV gets rude awakening

Editor's Choice Main Category: Crohn's / IBD Article Date: 26 Jul 2012 - 9:00 PDT

Current ratings for: Replacing Diseased Immune System With A Healthy One To Cure Chrohn's Disease

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Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract with symptoms of pain, fever, diarrhea and weight loss, which usually occurs in adolescents and young adults, but which can also occur during early childhood and older age. The Crohn's and Colitis Foundation of America estimates that more than 700,000 Americans are affected by the disease, although incident rates vary in different parts of the world, with incidence rates of 4 to 9 people per 100,000 in North America. 10% of Crohn's disease sufferers are affected by the most severe form for which there is no completely effective treatment.

Researchers have made substantial progress in the medical treatment of Crohn's disease over the past decade and a half, although even with the best immunosuppressive therapy, fewer than 50% of patients with a moderate to severe form of the disease achieve long-term relief. When Crohn's patients cease taking their medicines, their intestinal inflammation returns and patients who took prolonged courses of medicines that suppress the immune system were noted to have some severe infections.

The initial aim of the Crohn's Allogeneic Transplant Study (CATS) is to treat a small sample of patients with treatment-resistant Crohn's disease by transplanting matched bone marrow cells from a sibling or unrelated donor, which replaces a diseased or abnormal immune system with a healthy one.

The researchers hypothesized that an exchange of the immune system may be successful based on evidence that Crohn's is linked to abnormal immune responses to intestinal bacteria and to a loss of immune tolerance. CATS leading investigator George McDonald, M.D., a transplant researcher and gastroenterologist in the Hutchinson Center's Clinical Research Division says that there is solid evidence that genetic abnormalities in the immune regulatory system are related to Crohn's disease.

Even though the CATS clinical trial is a new direction for bone marrow transplantation, the procedure has already been used by Hutchinson Center researchers, who pioneered bone marrow and hematopoietic cell transplantation to treat blood cancers, and who have used allogeneic transplants to cure patients suffering from both leukemia and Crohn's disease with the result that the signs and symptoms of Crohn's disease subsequently disappeared. German studies have reported similar experiences.

Researchers have previously used autologous stem cell transplants in Crohn's disease patients, whereby the patient's own hematopoietic cells are removed and returned after high-dose chemotherapy to suppress the immune system. However, the benefits have only been partially permanent, which may be because the risk genes for Crohn's are still in the patient's body.

McDonald said:

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Replacing Diseased Immune System With A Healthy One To Cure Chrohn's Disease

Public release date: 23-Jul-2012 [ | E-mail | Share ]

Contact: Dean Forbes dforbes@fhcrc.org 206-667-2896 Fred Hutchinson Cancer Research Center

SEATTLE Researchers at Fred Hutchinson Cancer Research Center have opened a clinical trial to test the theory that giving a patient a new immune system can cure severe cases of Crohn's disease, a chronic inflammatory condition of the gastrointestinal tract.

Funded by an infrastructure grant from The Eli and Edythe Broad Foundation, the initial goal of the Crohn's Allogeneic Transplant Study (CATS) is to treat a small number of patients with treatment-resistant Crohn's disease by transplanting matched bone marrow cells from a sibling or unrelated donor. Such a bone marrow transplant replaces a diseased or abnormal immune system with a healthy one.

The idea of swapping out the immune system is based on evidence that Crohn's is related to an abnormal immune response to intestinal bacteria and a loss of immune tolerance. There is strong evidence that genetic abnormalities in the immune regulatory system are linked to the disease, according to CATS principal investigator George McDonald, M.D., a transplant researcher and gastroenterologist in the Hutchinson Center's Clinical Research Division.

Although the CATS clinical trial represents a new direction for bone marrow transplantation, the procedure has precedent. The Hutchinson Center, which pioneered bone marrow and hematopoietic cell transplantation to treat blood cancers, has used allogeneic transplants to cure patients who suffered from both leukemia and Crohn's, with subsequent disappearance of the signs and symptoms of Crohn's. Similar experiences have been reported from studies done in Germany.

While autologous stem cell transplants in which the patient's own hematopoietic cells are removed and then returned after high-dose chemotherapy is given to suppress the immune system have been used to treat Crohn's patients, the benefits have not always been permanent, probably because the risk genes for Crohn's are still present. "Autologous transplantation following chemotherapy beats the disease down but the Crohn's tends to come back," McDonald said.

More information about CATS can be found on the website http://www.cats-fhcrc.org, which includes a patient-eligibility questionnaire. In general, patients must be 18 to 60 years of age and have failed all existing conventional treatments but be healthy enough to undergo a bone marrow transplant. A matched donor of bone marrow must be found from either a sibling or an unrelated person who has volunteered to donate marrow. Private insurance must cover the cost of the transplant and related medical expenses.

Crohn's disease is usually discovered in adolescents and young adults but can occur from early childhood to older age. The incidence of Crohn's disease varies in different parts of the world with rates of four to nine persons per 100,000 people in North America. According to the Crohn's and Colitis Foundation of America, a leading advocacy organization, Crohn's may affect more than 700,000 Americans. Of those affected by Crohn's, about 10 percent suffer from the most severe form for which no treatment is completely effective.

Symptoms of Crohn's may include pain, fever, diarrhea and weight loss. Substantial progress has been made in medical treatment of Crohn's disease over the last 15 years. However, even with the best immunosuppressive therapy, less than half of patients with moderate to severe Crohn's achieve long-term relief. When patients stop taking their medicines, their intestinal inflammation returns. Some severe infections have been seen in patients who took prolonged courses of medicines that suppress the immune system.

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Clinical trial seeks to cure advanced Crohn's disease using bone marrow transplant

Study represents new use of bone marrow transplantation

Newswise SEATTLE Researchers at Fred Hutchinson Cancer Research Center have opened a clinical trial to test the theory that giving a patient a new immune system can cure severe cases of Crohns disease, a chronic inflammatory condition of the gastrointestinal tract.

Funded by an infrastructure grant from The Eli and Edythe Broad Foundation, the initial goal of the Crohns Allogeneic Transplant Study (CATS) is to treat a small number of patients with treatment-resistant Crohns disease by transplanting matched bone marrow cells from a sibling or unrelated donor. Such a bone marrow transplant replaces a diseased or abnormal immune system with a healthy one.

The idea of swapping out the immune system is based on evidence that Crohns is related to an abnormal immune response to intestinal bacteria and a loss of immune tolerance. There is strong evidence that genetic abnormalities in the immune regulatory system are linked to the disease, according to CATS principal investigator George McDonald, M.D., a transplant researcher and gastroenterologist in the Hutchinson Centers Clinical Research Division.

Although the CATS clinical trial represents a new direction for bone marrow transplantation, the procedure has precedent. The Hutchinson Center, which pioneered bone marrow and hematopoietic cell transplantation to treat blood cancers, has used allogeneic transplants to cure patients who suffered from both leukemia and Crohns, with subsequent disappearance of the signs and symptoms of Crohns. Similar experiences have been reported from studies done in Germany.

While autologous stem cell transplants in which the patients own hematopoietic cells are removed and then returned after high-dose chemotherapy is given to suppress the immune system have been used to treat Crohns patients, the benefits have not always been permanent, probably because the risk genes for Crohns are still present. Autologous transplantation following chemotherapy beats the disease down but the Crohns tends to come back, McDonald said.

More information about CATS can be found on the website http://www.cats-fhcrc.org, which includes a patient-eligibility questionnaire. In general, patients must be 18 to 60 years of age and have failed all existing conventional treatments but be healthy enough to undergo a bone marrow transplant. A matched donor of bone marrow must be found from either a sibling or an unrelated person who has volunteered to donate marrow. Private insurance must cover the cost of the transplant and related medical expenses.

Crohns disease is usually discovered in adolescents and young adults but can occur from early childhood to older age. The incidence of Crohns disease varies in different parts of the world with rates of four to nine persons per 100,000 people in North America. According to the Crohns and Colitis Foundation of America, a leading advocacy organization, Crohns may affect more than 700,000 Americans. Of those affected by Crohns, about 10 percent suffer from the most severe form for which no treatment is completely effective.

Symptoms of Crohns may include pain, fever, diarrhea and weight loss. Substantial progress has been made in medical treatment of Crohns disease over the last 15 years. However, even with the best immunosuppressive therapy, less than half of patients with moderate to severe Crohns achieve long-term relief. When patients stop taking their medicines, their intestinal inflammation returns. Some severe infections have been seen in patients who took prolonged courses of medicines that suppress the immune system.

The burden of this disease lays heavily on those who dont respond to any therapy, McDonald said.

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New Clinical Trial Seeks to Cure Advanced Crohn's Disease by Replacing a Diseased Immune System with a Healthy One

Public release date: 18-Jul-2012 [ | E-mail | Share ]

Contact: Sarah Dionne smdionne@partners.org 617-726-6126 Massachusetts General Hospital

One of the challenges to HIV vaccine development has been the lack of an animal model that accurately reflects the human immune response to the virus and how the virus evolves to evade that response. In the July 18 issue of Science Translational Medicine, researchers from the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard report that a model created by transplanting elements of the human immune system into an immunodeficient mouse addresses these key issues and has the potential to reduce significantly the time and costs required to test candidate vaccines.

"Our study showed not only that these humanized mice mount human immune responses against HIV but also that the ability of HIV to evade these responses by mutating viral proteins targeted by CD8 'killer' T cells is accurately reflected in these mice," says Todd Allen, PhD, senior author of the report. "For the first time we have an animal model that accurately reproduces critical host-pathogen interactions, a model that will help facilitate the development an effective vaccine for HIV." Recent studies by Allen's team and others have revealed that immune control of HIV is significantly limited by the ability of the virus to evade immune responses by rapidly mutating.

The traditional animal model for HIV research is the rhesus monkey, which can be infected with the related simian immunodeficiency virus (SIV). But differences in viral sequences between SIV and HIV, along with differences between the human and monkey immune systems, limit the ability of the SIV model to replicate directly key interactions between HIV and the human immune system. Development of an effective HIV vaccine will require a greater understanding of how human immune responses succeed or fail to control HIV.

The current study was designed to test the humanized BLT mouse, a model created by transplanting human bone marrow stem cells, along with other human tissue, into mice lacking a functioning immune system. Andrew Tager, MD, a co-author of the report and director of the MGH Humanized Mouse Program, explains, "Multiple researchers have contributed to dramatic improvements in the ability of humanized mice to model human diseases. Earlier studies with BLT mice performed at the University of Texas Southwestern Medical Center, the MGH and elsewhere have demonstrated that this particular humanized mouse model reproduces many aspects of the human immune response."

Timothy Dudek, PhD, of the Ragon Institute, lead author of the current study, adds, "Unlike normal mice, these humanized mice can be infected with HIV. But there has been little evidence regarding whether they reproduce the interaction between HIV and the human immune system, particularly the development of specific immune responses that exert control over HIV by targeting critical regions of the virus."

Tager's team at the MGH Center for Immunology and Inflammatory Diseases created groups of humanized BLT mice using cells and tissues from human donors with different alleles, or versions, of the immune system's HLA molecules, which flag infected cells for destruction by CD8 T cells. Particular HLA alleles, such as HLA-B57, are more common in individuals naturally able to control HIV, and some of the mice generated by Tager's group expressed this important protective allele.

Six weeks after the mice had been infected with HIV, the researchers found that the virus was rapidly evolving in regions known to be targeted by CD8 T cells. Their observation indicated that not only were the humanized mouse immune systems responding to HIV but also that the virus was mutating to avoid those responses in a manner similar to what is seen in humans. In mice expressing the protective HLA-B57 allele, just as in human patients who control viral levels, CD8 responses were directed against an essential region of the virus, preventing viral mutation and allowing the animals to more effectively contain HIV.

"We now know that these mice appear to replicate the specificity of the human cellular response to HIV and that the virus is attempting to evade these responses just as it does in humans," says Allen, an associate professor of Medicine at Harvard Medical School. "We are currently studying whether we can induce human HIV-specific immune responses in these animals by vaccination, which would provide a rapid, cost-effective model to test the ability of different vaccine approaches to control or even block HIV infection. If we can do this, we'll have a very powerful new tool to accelerate HIV vaccine development, one that also may be useful against other pathogens."

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Mouse with human immune system may revolutionize HIV vaccine research

ScienceDaily (July 17, 2012) Scientists at the California Institute of Technology (Caltech) pioneered the study of the link between irregularities in the immune system and neurodevelopmental disorders such as autism a decade ago. Since then, studies of postmortem brains and of individuals with autism, as well as epidemiological studies, have supported the correlation between alterations in the immune system and autism spectrum disorder.

What has remained unanswered, however, is whether the immune changes play a causative role in the development of the disease or are merely a side effect. Now a new Caltech study suggests that specific changes in an overactive immune system can indeed contribute to autism-like behaviors in mice, and that in some cases, this activation can be related to what a developing fetus experiences in the womb.

The results appear in a paper this week in the Proceedings of the National Academy of Sciences (PNAS).

"We have long suspected that the immune system plays a role in the development of autism spectrum disorder," says Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences at Caltech, who led the work. "In our studies of a mouse model based on an environmental risk factor for autism, we find that the immune system of the mother is a key factor in the eventual abnormal behaviors in the offspring."

The first step in the work was establishing a mouse model that tied the autism-related behaviors together with immune changes. Several large epidemiological studies -- including one that involved tracking the medical history of every person born in Denmark between 1980 and 2005 -- have found a correlation between viral infection during the first trimester of a mother's pregnancy and a higher risk for autism spectrum disorder in her child. To model this in mice, the researchers injected pregnant mothers with a viral mimic that triggered the same type of immune response a viral infection would.

"In mice, this single insult to the mother translates into autism-related behavioral abnormalities and neuropathologies in the offspring," says Elaine Hsiao, a graduate student in Patterson's lab and lead author of the PNAS paper.

The team found that the offspring exhibit the core behavioral symptoms associated with autism spectrum disorder -- repetitive or stereotyped behaviors, decreased social interactions, and impaired communication. In mice, this translates to such behaviors as compulsively burying marbles placed in their cage, excessively self grooming, choosing to spend time alone or with a toy rather than interacting with a new mouse, or vocalizing ultrasonically less often or in an altered way compared to typical mice.

Next, the researchers characterized the immune system of the offspring of mothers that had been infected and found that the offspring display a number of immune changes. Some of those changes parallel those seen in people with autism, including decreased levels of regulatory T cells, which play a key role in suppressing the immune response. Taken together, the observed immune alterations add up to an immune system in overdrive -- one that promotes inflammation.

"Remarkably, we saw these immune abnormalities in both young and adult offspring of immune-activated mothers," Hsiao says. "This tells us that a prenatal challenge can result in long-term consequences for health and development."

With the mouse model established, the group was then able to test whether the offspring's immune problems contribute to their autism-related behaviors. In the most revealing test of this hypothesis, the researchers were able to correct many of the autism-like behaviors in the offspring of immune-activated mothers by giving the offspring a bone-marrow transplant from typical mice. The normal stem cells in the transplanted bone marrow not only replenished the immune system of the host animals but altered their autism-like behavioral impairments.

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New evidence links immune irregularities to autism, mouse study suggests

Researchers at Brown University, along with colleagues at several universities, have learned how to analyze genetic markers in immune system cells. The technique allows the researchers to distinguish among several types of cancer, according to a release from the university by Mike Cohea.

The immune cells, called leukocytes, are present in the blood when a person has an illness. The new technique, described in two recent papers, lets scientists identify a unique chemical alteration to DNA of each type of leukocyte. By detecting these changes, call "methylation signatures," in a patients blood sample and applying a mathematical analysis, the researchers are able to determine the relative levels of different leukocytes and correlate those with specific diseases.

The release quotes Karl Kelsey, professor of pathology and laboratory medicine in the Warren Alpert Medical School of Brown University and a senior author on both papers, as saying, Its a way to more easily interrogate the immune system of a lot of people.

One of the papers was published in BMC Bioinformatics and the second one was published online in Cancer Epidemiology, Biomarkers, and Prevention. Our approach provides a completely novel tool for the study of the immune profiles of diseases where only DNA can be accessed, the authors wrote. That is, we believe this approach has utility not only in cancer diagnostics and risk-prediction, but can also be applied to future research (including stored specimens) for any disease where the immune profile holds medical information.

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Mix of Immune Cells Detects Cancer