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Making bone marrow transplants safer

New approach would use antibodies rather than radiation and chemotherapy June 7, 2016 | Editor's Pick Popular  By Hannah L. Robbins, Harvard Stem Cell Institute B.D. Colen/Harvard Stem Cell Institute Communications Rahul Palchaudhuri (left), postdoctoral fellow, and David Scadden, co-director of the Harvard Stem Cell Institute, look at real-time images of blood stem cells settling into bone marrow. Harvard Stem Cell Institute (HSCI) scientists have taken the first steps toward developing a treatment that would make bone marrow blood stem cell transplantation safer, and as a result, more widely available to the millions of people living with blood disorders such as sickle cell anemia, thalassemia, andAIDS. Bone marrow transplantation is the only curative therapy for these blood diseases. But for the new, transplanted stem cells to do their work, faulty stem cells must first be “evicted” or killed. Accomplishing that requires patients to endure chemotherapy and radiation, a vicious assault on the body with lifelong consequences. In a study recently published in the journal Nature Biotechnology, HSCI researchers at Harvard University and Massachusetts General Hospital (MGH), in collaboration with Boston Children’s Hospital and Dana-Farber Cancer Institute, all Harvard affiliates, have developed a nontoxic transplantation procedure using antibodies to specifically target blood stem cells in mice, an approach they hope will make blood stem cell transplants for these patients far less toxic. The new treatment removes more than 98 percent of blood stem cells, making it as effective as chemotherapy and radiation, researchers said. “Instead of using non-targeted drugs that have lots of collateral damage, we thought we could take advantage of the precision of the immune system, in particular antibodies,” said David Scadden, co-director of HSCI, the Gerald and Darlene Jordan Professor of Medicine, and [...]

Researchers Discover A New Mechanism of Proteins to Block HIV

Certain IFITM proteins block and inhibit cell-to-cell transmission of HIV Sept. 25, 2015 By Sheena Rice COLUMBIA, Mo. – There is little doubt that the Human Immunodeficiency Virus, or HIV, is devastating. More than 1.2 million people in the United States are living with HIV and more than 47,000 people are diagnosed annually. Now, University of Missouriresearchers have made a discovery in how specialized proteins can inhibit the virus, opening the door for progress in the fight against HIV and for the production of advanced therapeutics to combat the disease. Human cells express Interferon Induced Transmembranes (IFITM) proteins that possess antiviral characteristics. These proteins have been shown to inhibit a number of viruses including influenza A, West Nile, Dengue fever and Ebola. In his study, Shan-Lu Liu, an associate professor in the Department of Molecular Microbiology and Immunology in the School of Medicine and an investigator in the Bond Life Sciences Center at MU, targeted IFITM proteins and their antiviral function. “We have long understood that IFITM proteins have antiviral functions, but until now we did not know exactly how the proteins specifically inhibited the transmission of HIV” Liu said. “We’ve known that HIV-1, the most common HIV strain, can be transmitted from cell to cell or through a cell-free transmission in which the virus floats freely. Our research discovered that IFITM proteins can help inhibit the viral cell-to-cell infection, which is the most efficient way that HIV spreads.” Jingyou Yu, a doctoral student in MU’s pathobiology graduate program, conducted experiments to show that IFITM proteins, particularly IFITM2 and IFITM3, block HIV cell-to-cell transmission. Yu then partnered with Minghua Li, who is also a graduate student in pathobiology, and discovered that IFITM proteins specifically interact with [...]

Scientists Say Fetal Tissue Essential for Medical Research

Wed, 08/12/2015 - 10:00am Collin Binkley and Carla K. Johnson, Associated Press In this Aug. 10, 2015, photo, Dr. Akhilesh Pandey, a researcher at Johns Hopkins University, poses alongside a mass spectrometer in his laboratory in Baltimore. Pandey's research analyzes both adult and fetal tissue, and by identifying which proteins are present, he can get clues that could be used to help detect cancer in adults earlier. (AP Photo/Patrick Semansky)The furor on Capitol Hill over Planned Parenthood has stoked a debate about the use of tissue from aborted fetuses in medical research, but U.S. scientists have been using such cells for decades to develop vaccines and seek treatments for a host of ailments, from vision loss to cancer and AIDS.Anti-abortion activists triggered the uproar by releasing undercover videos of Planned Parenthood officials that raised questions of whether the organization was profiting from the sale of fetal tissue. Planned Parenthood has denied making any profit and said it charges fees solely to cover its costs. University laboratories that buy such cells strongly defend their research, saying tissue that would otherwise be thrown out has played a vital role in lifesaving medical advances and holds great potential for further breakthroughs. Fetal cells are considered ideal because they divide rapidly, adapt to new environments easily and are less susceptible to rejection than adult cells when transplanted. "If researchers are unable to work with fetal tissue, there is a huge list of diseases for which researchers would move much more slowly, rather than quickly, to find their cause and how they can be cured," Stanford University spokeswoman Lisa Lapin said in an email. From 2011 through 2014 alone, 97 research institutions - mostly universities and hospitals - received a [...]

First Self-injectable HIV Antibody

Tue, 08/11/2015 - 11:45 am Lindsay Hock, Editor Digital illustration of HIV virus in blood stream in color background. Image: RAJ CREATIONZS/ShutterstockHIV has been categorized as “the most intelligent virus in centuries.” This is due to the virus' capability to hide in a reservoir inside organs and, also, because it mutates at a very high rate due inside CD4 cells. Essentially, the virus converts its RNA to DNA and makes sloppy copies of itself; and each copy is different from the origin and represents a resistance strain.However, now there’s a new hope for those suffering from HIV infection: the first self-injectable antibody, PRO 140, developed by CytoDyn Inc., has documented a 98% success rate in a Phase 2b clinical trial for patients with HIV. In a monotherapy study, some HIV patients using PRO 140 are experiencing a completely suppressed viral load for about 11 months, according to the company. And PRO 140 could be commercialized in 2017 if it receives positive results from an upcoming Phase 3 trial. Current HIV treatment and the positives of PRO 140 Currently there are over 1.2 million individuals infected with HIV in the U.S., and about 56,000 new infections are reported each year. Worldwide, 33.4 million individuals are infected with HIV, with 2.7 million new infections annually reported. With the growing number of infections, about $15 billion is spent on therapy for HIV annually, in hopes to stop the spread of the virus. Highly Active Anti-Retroviral Therapy, better known as HAART, is the current standard of care for HIV. HAART is a three drug regiment from two different classes and is taken daily for life. Since the introduction of HAART in 1996 by Dr. David Ho, HIV is no [...]

Magnetic Nanoparticles Could Be Key To Effective Immunotherapy

New method moves promising strategy closer to clinical use Release Date: July 15, 2015 FAST FACTS: Immunotherapy is based on the idea of training the body’s own immune cells to better combat cancer, infections and other diseases. A major challenge to its success has been the inability to produce enough trained immune cells to have a curative and lasting impact. Researchers have found a way to efficiently produce large numbers of trained immune cells using magnetic nanoparticles. A graphic showing a process for producing large numbers of activated, customized T cells using magnetic nanoparticles and a column. Credit: Karlo Perica/Johns Hopkins Medicine In recent years, researchers have hotly pursued immunotherapy, a promising form of treatment that relies on harnessing and training the body’s own immune system to better fight cancer and infection. Now, results of a study led by Johns Hopkins investigators suggests that a device composed of a magnetic column paired with custom-made magnetic nanoparticles may hold a key to bringing immunotherapy into widespread and successful clinical use. A summary of the research, conducted in mouse and human cells, appears online July 14 in the journalACS Nano. The Johns Hopkins team focused on training and rapidly multiplying immune system white blood cells known as T cells because of their potential as an effective weapon against cancer, according toJonathan Schneck, M.D., Ph.D., a professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine’s Institute for Cell Engineering. “The challenge has been to train these cells efficiently enough, and get them to divide fast enough, that we could use them as the basis of a therapy for cancer patients. We’ve taken a big step toward solving that problem,” he says. In a [...]

Scientists Unravel Elusive Structure of HIV Protein

June 30, 2015 by Jeff Sossamon COLUMBIA, Mo. – HIV, or human immunodeficiency virus, is the retrovirus that leads to acquired immunodeficiency syndrome or AIDS. Globally, about 35 million people are living with HIV, which constantly adapts and mutates creating challenges for researchers. Now, scientists at the University of Missouri are gaining a clearer idea of what a key protein in HIV looks like, which will help explain its vital role in the virus’ life cycle. Armed with this clearer image of the protein, researchers hope to gain a better understanding of how the body can combat the virus with the ultimate aim of producing new and more effective antiviral drugs. The HIV capsid protein, shown above in an array of hexagons, plays a critical role in the virus’ life cycle. Mizzou researchers recently developed the most complete model yet of this vital protein. Image by Karen Kirby and Anna Gres. In recent years, scientists have used various techniques to determine the structure of the capsid protein, which is the building block of an inner shell of HIV. Until now, the clearest image had been of a mutated protein. Stefan Sarafianos, an associate professor of molecular microbiology and immunology and the Chancellor’s Chair of Excellence in molecular virology in the University of Missouri School of Medicine, and his team captured long sought detailed images of the capsid protein in its natural state. “The capsid shell acts as an ‘invisibility cloak’ that hides the virus’ genetic information, the genome, while it is being copied in a hostile environment for the virus,” said Sarafianos, who also holds an appointment in the Department of Biochemistry in the College of Agriculture, Food and Natural Resources and serves as a researcher at [...]

Stem cell gene therapy developed at UCLA holds promise for eliminating HIV infection

Method modifies immune cells to attack the virus, could be used to treat other diseases Mirabai Vogt-James | June 30, 2015 UCLA Broad Stem Cell Research CenterThe scientists, led by Jerome Zack (left) and Scott Kitchen, found that the technique decreased HIV levels in mice by 80 to 95 percent. Scientists at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research are one step closer to engineering a tool that could one day arm the body’s immune system to fight HIV — and win. The new technique harnesses the regenerative capacity of stem cells to generate an immune response to the virus. The findings were published today in the journal Molecular Therapy. “We hope this approach could one day allow HIV-positive individuals to reduce or even stop their current HIV drug regimen and clear the virus from the body altogether,” said Scott Kitchen, the study’s lead author and a member of the Broad Stem Cell Research Center. “We also think this approach could possibly be extended to other diseases.” Kitchen also is a member of the UCLA AIDS Institute and an associate professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA. Kitchen and his colleagues were the first to report the use of an engineered molecule called a chimeric antigen receptor, or CAR, in blood-forming stem cells. Blood-forming stem cells are capable of turning into any type of blood cell, including T cells, the white blood cells that are central to the immune system. In a healthy immune system, T cells can usually rid the body of viral or bacterial infection. But HIV is too strong and mutates too rapidly for T [...]

Filling in the gaps of HIV

By Caleb O’Brien | MU Bond Life Sciences Center The HIV capsid protein (shown above in an array of hexagons) plays a critical role in the virus life cycle. Bond LSC researchers recently developed the most complete model yet of this vital protein.  Image by Karen Kirby and Anna GresSeeing the whole picture can mean a lot when it comes to figuring out HIV. Researchers at the University of Missouri Bond Life Sciences Center are gaining a clearer idea of what a key protein in HIV looks like, which will help explain the flexible protein’s vital role in the virus life cycle. The protein the researchers imaged is a building block that forms the virus’ capsid, a protective shell surrounding the virus’ genes. The journal Science published their findings online June 4. Stefan Sarafianos“The capsid acts as an invisibility cloak that hides the virus’ genetic information, the genome, while it is being copied in a hostile environment for the virus,” said Stefan Sarafianos, a virologist at Bond LSC and lead author of the study. “Fine-tuned capsid stability is critical for successful infection: too stable a capsid shell and the cargo is never delivered properly; not stable enough and the contents are detected by our immune defenses, triggering an antiviral response. Capsid stability is a key to the puzzle, and to solve it you have to understand its structure.” This is the most complete model yet of an HIV-1 capsid protein. In a virus, the protein combines in groups of five or six — called pentamers and hexamers, respectively — that assemble into a mosaic that forms the capsid shell. Roughly 1,500 copies of the protein, grouped into about 250 hexamers and 12 pentamers, comprise the capsid. The protein [...]

Wild chimps teach scientists about gene that encodes HIV-fighting protein

Part of a gene variant present in some wild African chimps is nearly identical to a section of an analogous gene version found in HIV-infected humans who are uncharacteristically slow to progress to full-blown AIDS. MAY 282015 Stanford researchers discovered that some of the chimpanzees in the Gombe Stream National Park, made famous by primatologist Jane Goodall, have a genetic varient that may help prevent them from succumbing to the primate equivalent of HIV. Emily Wroblewski A gene variant in chimpanzees in a Tanzanian wildlife preserve probably protects them from rapidly succumbing to the primate equivalent of HIV, Stanford University School of Medicine scientists have discovered. A gene variant is a naturally occurring difference in the DNA sequence of a gene. Part of the chimp variant strongly resembles that of an analogous human variant known to slow the human immunodeficiency virus’ progression to AIDS. The wild chimps inhabit Gombe Stream National Park, a 13.5-square-mile preserve where they have been continuously observed from afar since famed primatologist Jane Goodall, PhD, began monitoring them more than 50 years ago. The gene in question is subject to evolutionary pressures that normally cause it to change rapidly over evolutionary time, resulting in many variants with diverse sequences. So the striking similarity of a section of the chimp and a section of the human variant implies two things, said Peter Parham, PhD, professor of structural biology and of microbiology and immunology. First, hominids have been fighting off HIV-like viruses at least since the two related species diverged some 5 million years ago. Second, because that particular section of the gene variant hasn’t changed much since then, it probably plays an important role in increased survival among those inheriting it. “Only a [...]

City of Hope Launches Stem Cell Therapy Clinic to Fight Incurable Disease in New Ways

March 23, 2015 11:30 AM Eastern Daylight Time DUARTE, Calif.--(BUSINESS WIRE)--In the field of cancer, patients have had surgery, chemotherapy and radiation therapy as options. Now, as City of Hope officially opens the Alpha Clinic for Cell Therapy and Innovation, patients battling cancer and other life-threatening diseases have another option: stem cell-based therapy. “We are in a new era of cellular therapy” The Alpha Clinic, which officially opened March 19, is funded by an $8 million, five-year grant from the California Institute for Regenerative Medicine that will be supplemented by matching funds from City of Hope. It will combine the uniquely patient-centered care for which City of Hope is known with the most innovative, stem cell-based therapies being studied to date. The approach is expected to revolutionize the treatment of not only cancer, but also AIDS and other life-threatening diseases. “We are in a new era of cellular therapy,” said John Zaia, M.D., the Aaron D. Miller and Edith Miller Chair in Gene Therapy, chair of the Department of Virology and principal investigator for the stem cell clinic. “The California Institute for Regenerative Medicine recognizes this, and they have been leading the field. Alpha Clinics like ours aim not only to provide research to benefit patients in the future, but also to get these innovative treatments running in real-life clinics to benefit patients now.” The launch of City of Hope’s Alpha Clinic comes a decade after Californians voted to found the California Institute for Regenerative Medicine, making a commitment to investigate stem cell therapies in the laboratory. Now these therapies are ready for clinical trials, and City of Hope is home to one of three Alpha Clinics in the state. The other two are at [...]