UNC researchers ID cell where HIV persists despite treatment, new target for cure research – News & Observer

UNC researchers ID cell where HIV persists despite treatment, new target for cure research News & Observer But researchers in the Division of Infectious Diseases at the UNC School of Medicine have found that the virus still persists in HIV-infested macrophages large white blood cells found in tissues throughout the body, including the liver, lungs, bone ... and more »

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UNC researchers ID cell where HIV persists despite treatment, new target for cure research - News & Observer

Immune cells play surprising role in steady heartbeat – Science News

Immune system cells may help your heart keep the beat. These cells, called macrophages, usually protect the body from invading pathogens. But a new study published April 20 in Cell shows that in mice, the immune cells help electricity flow between muscle cells to keep the organ pumping.

Macrophages squeeze in between heart muscle cells, called cardiomyocytes. These muscle cells rhythmically contract in response to electrical signals, pumping blood through the heart. By plugging in to the cardiomyocytes, macrophages help the heart cells receive the signals and stay on beat.

Researchers have known for a couple of years that macrophages live in healthy heart tissue. But their specific functions were still very much a mystery, says Edward Thorp, an immunologist at Northwestern Universitys Feinberg School of Medicine in Chicago. He calls the studys conclusion that macrophages electrically couple with cardiomyocytes paradigm shifting. It highlights the functional diversity and physiologic importance of macrophages, beyond their role in host defense, Thorp says.

Matthias Nahrendorf, a cell biologist at Harvard Medical School, stumbled onto this electrifying find by accident.

Curious about how macrophages impact the heart, he tried to perform a cardiac MRI on a mouse genetically engineered to not have the immune cells. But the rodents heartbeat was too slow and irregular to perform the scan.

Immune cells called macrophages (green) squeeze in between heart cells (red) in an area of the heart called the atrioventricular node, as seen in this reconstruction of a human AV node. This node is a cluster of muscle fibers that electrically connects the upper and lower chambers of the heart.

These symptoms pointed to a problem in the mouses atrioventricular node, a bundle of muscle fibers that electrically connects the upper and lower chambers of the heart. Humans with AV node irregularities may need a pacemaker to keep their heart beating in time. In healthy mice, researchers discovered macrophages concentrated in the AV node, but what the cells were doing there was unknown.

Isolating a heart macrophage and testing it for electrical activity didnt solve the mystery. But when the researchers coupled a macrophage with a cardiomyocyte, the two cells began communicating electrically. Thats important, because the heart muscle cells contract thanks to electrical signals.

Cardiomyocytes have an imbalance of ions. While in the resting state, there are more positive ions outside the cell than inside, but when a cardiomyocyte receives an electrical signal from a neighboring heart cell, that distribution switches. This momentary change causes the cell to contract and send the signal on to the next cardiomyocyte.

Scientists previously thought that cardiomyocytes were capable of this electrical shift, called depolarization, on their own. But Nahrendorf and his team found that macrophages aid in the process. Using a protein, a macrophage hooks up to a cardiomyocyte. This protein directly connects the inside of these cells to each other, allowing macrophages to transfer positive charges, giving cardiomyocytes a boost kind of like with a jumper cable. This makes it easier for the heart cells to depolarize and trigger the heart contraction, Nahrendorf says.

With the help of the macrophages, the conduction system becomes more reliable, and it is able to conduct faster, he says.

Nahrendorf and colleagues found macrophages within the AV node in human hearts as well but dont know if the cells play the same role in people. The next step is to confirm that role and explore whether or not the immune cells could be behind heart problems like arrhythmia, says Nahrendorf.

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Immune cells play surprising role in steady heartbeat - Science News

For stem cell treatments, patients, doctors, scientists must collaborate – The San Diego Union-Tribune

Stem cell research begins with scientists, passes on to physicians and ends up with patients.

But those roles arent as separate as they seem, said speakers Thursday at a special meeting held by the California Institute for Regenerative Medicine, the states stem cell agency, and UC San Diego.

The agency is beginning a statewide tour to discuss the progress of its treatments through the lengthy research and clinical trial process. One priority is to make sure all those involved understand each others needs, and how they can help.

Speaker David Higgins has multiple roles built into his life. A San Diegan with Parkinsons disease, Higgins sits on CIRMs governing board.

Patient input is heard throughout CIRM, Higgins said, addressing the audience of more than 100 at the Sanford Consortium for Regenerative Medicine on Torrey Pines Mesa.

Patient advocates sit on reviews for grant funding, Higgins said. Nothing ever goes out the door without it being screened through the eyes of a patient advocate.

Patients can now take a much more active role in managing their illness and advocate for others, Higgins said, because doctors now recognize that treating disease is a partnership.

Now were looking at a two-way relationship, Higgins said. I dont know a single physician that Ive ever talked to who doesnt welcome this, Higgins said.

And in the long run, nobody can escape patienthood, said Dr. Catriona Jamieson, an oncologist-researcher at UCSD Moores Cancer Center.

Were all going to be patients, were all going to be health care users, Jamieson said. I dont see the patient term as in any way stigmatizing, because its part of using our health care system.

Making sure these roles are harmonized is important to CIRM, which has about $800 million left of the $3 billion given by California voters in 2004 in Proposition 71.

And while CIRM cant formally lobby on the issue, those who support the agency recognize they need public support if they want more money from taxpayers.

Jamieson said CIRM has helped her research, her UCSD colleagues and patients by grants and funding alpha stem cell clinics, including one at UCSD. These clinics help translate science into patient care, and help scientists and doctors share ideas and resources.

What we know so far is that great medicine requires great science, said Jamieson, who specializes in blood cancers.

Audience member Adrienne Shapiro was there as a patient advocate for sickle cell disease. Shes a carrier of the trait, and her daughter, Marissa Cors, has the disease. CIRM has funded a program to develop a better bone marrow transplant to treat the disease.

Cors said one of her main issues is dealing with the pain sickle cell disease causes her.

The pain medications are really the key at this particular point in the journey, Cors said, hesitating slightly in discussing the course of her disease.

Cors said shes hopeful that the CIRM program helps others.

Im looking for something effective for the community, Cors said.

bradley.fikes@sduniontribune.com

(619) 293-1020

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For stem cell treatments, patients, doctors, scientists must collaborate - The San Diego Union-Tribune

Immune-Based Therapy Shows Early Promise Against MS – Montana Standard

THURSDAY, April 20, 2017 (HealthDay News) -- An experimental immune-system therapy appears safe for people with progressive forms of multiple sclerosis. And it may ease symptoms in some, a preliminary study suggests.

The findings are based on just six patients, and the Australian researchers stressed that a lot of work still lies ahead.

But they were encouraged that this new approach to MS had no major side effects. In addition, three of the six patients showed symptom improvements, including reduced fatigue and better mobility.

It's not clear, however, what to make of those improvements, said Bruce Bebo, executive vice president of research for the National Multiple Sclerosis Society.

The study was a "phase 1" trial, meaning it was designed only to test the therapy's safety.

"Based on this very preliminary study, the therapy appears safe," said Bebo, who was not involved in the research.

"But I'd be even more cautious in drawing any conclusions about the clinical improvements," he stressed.

Larger, rigorous clinical trials are needed to show whether the treatment truly works, Bebo said.

Multiple sclerosis is caused by a misguided immune system attack on the protective sheath around nerve fibers in the spine and brain. Depending on where the damage occurs, symptoms can include vision problems, muscle weakness, numbness and difficulty with balance and coordination.

Most people with MS are initially diagnosed with the "relapsing-remitting" form, which means that symptoms flare up for a time and then ease.

The new study involved patients with progressive MS, where the disease steadily worsens without periods of recovery.

Most had the "secondary" progressive form -- which means they initially had relapsing-remitting MS, but it worsened. One patient had progressive MS from the start, which is known as "primary" progressive MS.

The patients agreed to try a treatment never studied in MS, said study co-author Rajiv Khanna, of the QIMR Berghofer Medical Research Institute in Brisbane, Australia.

The approach is known as "adoptive" immunotherapy, where a patient's own immune system T cells are genetically tweaked to fight an enemy -- such as cancer cells.

Khanna's team took samples of the MS patients' T cells, then altered the cells to boost their ability to recognize and attack the Epstein-Barr virus. Those T cells were infused back into the patients' blood, at gradually escalating doses over six weeks.

Epstein-Barr is a common virus that infects most people at some point. But researchers suspect it plays a role in MS in some people.

According to Khanna, there is also evidence that MS progression correlates with Epstein-Barr "activation" in the body. The aim of the T-cell therapy is to "clear out" B cells -- another type of immune system cell -- that are infected with Epstein-Barr.

Over six months, the researchers said, none of the patients suffered serious side effects from the treatment.

In addition, three showed symptom improvements within two to eight weeks of their first T-cell infusion.

The findings are scheduled for presentation at the annual meeting of the American Academy of Neurology, April 22-28, in Boston.

The biology behind the T-cell therapy is not fully clear, Bebo said. Although Epstein-Barr is suspected as one factor in driving the initial development of MS, even that is not established, he said.

On the other hand, there is evidence that B cells drive inflammation in MS, Bebo said.

In fact, a new MS drug approved just last month works by targeting B cells, he noted.

That drug, called Ocrevus (ocrelizumab), is the first drug ever approved for primary progressive MS in the United States. It can also be used for the relapsing-remitting form.

Bebo said he suspects that if the experimental T-cell therapy has benefits in MS, it might be because it clears out B cells.

Even if the approach proves effective, there are practical hurdles in delivering a therapy like that, Bebo pointed out.

Khanna said his team is collaborating with a U.S. biotech company to see if the treatment process can be refined -- by creating "off-the-shelf" versions of Epstein-Barr-fighting T cells, for example.

Bebo emphasized the bigger picture: The new drug ocrelizumab was just approved and other treatments are in the pipeline.

"This is one of many approaches being tested," Bebo said. "We're learning more about MS progression all the time. So the future looks bright."

Study results presented at meetings are usually considered preliminary until published in a peer-reviewed medical journal.

The U.S.-based National MS Society has more on treating MS.

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Immune-Based Therapy Shows Early Promise Against MS - Montana Standard

PolarityTE (COOL) Signs Manufacturing Agreement with Cell Therapy and Regenerative Medicine – StreetInsider.com

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PolarityTE, Inc. (NASDAQ: COOL) announces the signing of a manufacturing agreement with Cell Therapy and Regenerative Medicine at the University of Utah School of Medicine. CTRM is the established manufacturer of hematopoietic stem cell transplants for renowned institutions of the Salt Lake region such as the Huntsman Cancer Institute and Primary Children's Hospital. In addition, CTRM manufactures a variety of regenerative medicine products, is FACT accredited, and has technical expertise in current Good Tissue Practice (cGTP) and current Good Manufacturing Practice (cGMP).

Denver Lough, MD, PhD, Chairman and CEO, stated, "This agreement with CTRM should provide PolarityTE with rapid clinical translation of the promising products we are developing, and takes us one step closer to achieving our goal of clinical application of our launch product, SkinTE. As we prepare for market entry in 2018, our established relationship with CTRM creates a springboard for the anticipated scale-up to address the large burn and chronic wound markets, with the pursuit of our own independent manufacturing facility. Plans are solidifying for a unique solution to both commercial and emergent relief manufacturing of SkinTE and future Polarity products. Our goal is not only to meet demand, but also to be able to deliver promptly around the globe when urgent response is needed."

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PolarityTE (COOL) Signs Manufacturing Agreement with Cell Therapy and Regenerative Medicine - StreetInsider.com

HER2-Specific CAR T-Cell Therapy Active in Progressive … – Cancer Network

Administration of autologous HER2-specific chimeric antigen receptor (CAR)-modified virus specific T Cells (VSTs) was safe and had clinical benefit for some patients with progressive glioblastoma, a disease with limited effective therapeutic options.

Results of a small phase I study of this monotherapy were published in JAMA Oncology, by Nabil Ahmed, MD, MPH, of Baylor College of Medicine in Houston, and colleagues.

CAR T-cell therapies are an attractive strategy to improve the outcomes for patients with glioblastoma, they wrote. In our study, we infused HER2-CAR VSTs intravenously because T cells can travel to the brain after intravenous injections, as evidenced by clinical responses after the infusion of tumor-infiltrating lymphocytes for melanoma brain metastasis and by detection of CD19-CAR T cells in the cerebrospinal fluid of patients with B-precursor leukemia.

The study included 17 patients with progressive HER2-positive glioblastoma (10 patients aged 18 or older; 7 patients younger than 18). Patients were given one or more infusions of autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs. Six patients were given multiple infusions.

Infusions were well tolerated with no dose limiting toxicities presenting. Two patients had grade 2 seizures and/or headaches, which the researchers wrote were probably related to the T-cell infusion.

Although HER2-CAR VSTs did not expand, they were detected in the peripheral blood for up to 12 months after the infusion.

Although we did not observe an expansion of HER2-CAR VSTs in the peripheral blood, T cells could have expanded at glioblastoma sites. At 6 weeks after T-cell infusion, the MRI scans of patients 3, 7, 10, 16, and 17 showed an increase in peritumoral edema, the researchers wrote. Although these patients were classified as having a progressive disease, it is likely that the imaging changes for some of these patients were due to inflammatory responses, indicative of local T-cell expansion, especially since these patients survived for more than 6 months.

Only 16 of the 17 patients were evaluable for response. Patients underwent brain MRI 6 weeks after T-cell infusion. One patient had a partial response for longer than 9 months and seven patients had stable disease for between 8 weeks to 29 months. Three patients with stable disease are alive without any evidence of progression from 24 to 29 months of follow-up. Eight patients progressed after the infusion.

The median overall survival was 11.1 months from the first T-cell infusion and 24.5 months from diagnosis.

The researchers noted that the inclusion of children in the study, who have a better prognosis than adults, may have affected the results; however, there was no significant difference between the survival probability for children and that for adults in this clinical study.

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HER2-Specific CAR T-Cell Therapy Active in Progressive ... - Cancer Network