MicroRNAs May Be Key to Better Immunotherapy for Mesothelioma – Surviving Mesothelioma

Australian scientists say it may be possible to artificially reduce the levels of a protein that helps mesothelioma tumors hide from the immune system.

The new research published in the Journal of Thoracic Oncology could open the door to more effective immunotherapy treatments for pleural mesothelioma.

A cell surface protein called PD-L1 is key to the effectiveness of several new immunotherapy drugs including Keytruda (pembrolizumab), Opdivo (nivolumab), and avelumab.

An estimated 40 percent of mesothelioma tumors overexpress this protein, which is part of the processthat allows several different kinds of cancers to escape detection and attack by the immune system.

Now, a new study conducted at the Asbestos Diseases Research Institute at the University of Sydney has revealed more about the mechanismsbehind PD-L1 expression in malignant mesothelioma. The results suggest that it may be possible to downregulate this tumor-protecting protein from the inside out.

MicroRNAs are short, single-stranded RNA molecules that regulate gene expression,which, in turn, governs all kinds of cellular processes.

Among 72 test subjects with malignant pleural mesothelioma, the Australian team found that 18 (25%) tested positive for PD-L1 overexpression. The PD-L1-positive mesothelioma patients showed key differences in the action of certain microRNAs.

In the same patient series, PD-L1 expression was also associated with downregulation of microRNAs previously shown to have tumour suppressor activity in malignant pleural mesothelioma, writes Steven C. Kao, the lead author on the paper.

When the researchers manipulated these microRNAs by transfecting mesothelioma cell lines with artificial microRNAs or mimics, they found that they were able to downregulate the expression of the PD-L1 protein.

The new findings are significant because mesothelioma patients who overexpress PD-L1 have poorer outcomes than patients who dont.

The Australian researchers found that test subjects whose mesothelioma tumors tested positive for PD-L1 were more likely to have either the biphasic or sarcomatoid subtype of mesothelioma and tended to experience shorter survival.

The median overall survival of the PD-L1-expressing mesothelioma patients was just 4 months, compared to 9.2 months for the mesothelioma patients with negative PD-L1 staining.

Together, these data suggest that tumour suppressor microRNAs contribute to the regulation of PD-L1 expression in malignant pleural mesothelioma, writes Dr. Kao.

Source:

Kao, SC, et al, Tumour suppressor microRNAs contribute to the regulation of PD-L1 expression in malignant pleural mesothelioma, June 16, 2017, Journal of Thoracic Oncology, Epub ahead of print

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MicroRNAs May Be Key to Better Immunotherapy for Mesothelioma – Surviving Mesothelioma

Four of the Most Misused Terms in Alternative Medicine – ATTN:

A lot of talk about alternative medicine invovles taking legitimate medical terms and infusing them with dubious new definitions to sell some often sketchy products. The incorrect use of pseudoscientificlanguage lends credibility to concepts that aren’t actually accepted by the medical community, turning people away from scientifically proven medical treatment. It also makes its practitioners a lot of money.

Here are some of the terms that are most commonly used and misused by alternative medicine gurus, natural products websites, dubious doctors, holistic healers, and all those purporting to treat illnesses with things other than science.

Perhaps no word is more misused by the alternative medicine industry than “toxin.”

In the scientific sense, a toxin is a poisonous substancethat can have either a negative or positive effect on tissue, depending on dosage and chemical makeup. Scorpion venom, snake venom, andBotulinum toxin are all examples of naturally occurring compounds thatare extremely poisonous, but also have proven uses in science and medicine.

However, “toxins” in the alternative sense are defined only as bad substances that get into your body and cause a variety of maladies.

The popular site “Mind Body Green” claims that being “surrounded by too many toxins” causes fatigue, weight gain, muscle aches, and constipation. David Wolfe, an alternative medicine guru known for his prolific Facebook memes, lists “signs that you need to flush toxins” as lethargy, skin problems, headaches, and feeling hot. Toxins are also blamed for everything from belly fat to autoimmune diseases.

At no point do these types ever attempt to define thechemical makeup of a toxin, the mechanisms by which they work, or how we can be surrounded by toxins in our air, food and water without being dead. Toxins are simply bad, and you need to get rid of them. Which brings us to…

Alternative medicine retailers sell countlesscleanses and detox diets meant to flush you of the toxins that have built up in your body.

Colon cleanse detoxes are among the most popular, but you can do a cleanse for the liver, kidneys, lymph nodes, or anything else. You can go on a cleansing diet, or do a”salt water flush” or a “dual action cleanse” using anything from juices and teas to powders and pills to over thecounter laxatives to bentonite clay to coffee enemas. You can get toxins pulled out of your feet, skin, or mouth, and you can sweatthem out or freeze them.And you can do it at a clinic, or at home.

The benefits ofcleansing are said to be truly miraculous. The “Global Healing Center” claims cleansing will improve digestion, increase your energy, burn off pounds, promote general health, and above all, purge you of the toxins that can only be removed by cleansing.

What cleansing proponents don’t talk anywhere near as much about are the risks of cleansing. The vast majority of cleanses simply speed up and increase waste elimination, whichcan cause dehydration, cramps, and lightheadedness. And more invasive forms, such as enemas, can have severecomplications, including “perforating the bowel, serious infections, electrolyte imbalances, kidney problems and heart failure.”

Beyond that, the efficacy of cleansing has never been proven, and many cleanse products are known to be fraudulent. Of course, your body already has an all naturalway to cleanse: going to the bathroom. And while detoxing is an actual medical term, it’s only done for people with heavy metal poisoning (though detox products are also sold for that) and coming down from a drug addiction.

Given the glut of toxins in our environment, it’s only natural that we should want to boost our immune systems in order to stave off disease.

The alternative medicine sphere is filled with immune-boosting foods, supplements, vitamins, and drinks. But do they do anything? And more importantly: do you want them to?

While charging up the immune system to fight illness sounds plausible, science writer Brian Dunning has a better analogy for how it should work: a teeter-totter. “If your immune system is compromised or otherwise weakened, one side of the teeter totter sags, and your body becomes more easily susceptible to infection,” Dunning writes. “Conversely, if your immune system is overactive, the other side of the teeter totter sags, and the immune system attacks your own healthy tissues.”

The result of an overactive immune system is not health but auto-immune disease. Fortunately, most commonly available immune system boosting products aren’t powerful enough to do anything other than deliver an easily excreted megadose of vitamins.

Generally, experts agree that the best way to keep your immune system running smoothly is to lead a healthy lifestyle, get enough sleep, eat well, and not smoke.

From a scientific standpoint, energy is defined by Dictionary.com as “power derived from the utilization of physical or chemical resources, especially to provide light and heat or to work machines.” There are various ways to measure the transfer of energy from one body to another, and it can be consumedas food by living things, liquid fuel by machines, or in nuclear fusion by stars.

However, in alternative medicine,energy is not a measurable unit of work, but an immeasurable field of life force. It goes by a variety of names, including Reiki, therapeutic touch, prana, Qigong, orgone, healing touch, quantum healingand so on. Each one of these is slightly different, but operates on the same principles: that a skilled healer can use their life energy to heal sickness in others, either directly or indirectly.

Unlike many misused medical terms like cleansing and toxins, manyof theconcept related to energy medicine have been studied in clinical trials. But because “life energy” is impossible to detect, it’s difficult to design proper studies that can be double blinded and controlled. As one paper puts it, “testing implausible treatments in clinical trials is wasteful and perhaps even detrimental.”

A positive attitude opens you to the flow of life. It defines the energy you send out and shapes your circumstances.

A few studies have shown at least some effect from touch therapy in reducing low-grade pain. This fits with already established research on the power of touch to increase mental and physical health. If some forms of energy healing do work, it’s because touch has a powerful effect on human physiology, not because of invisible energy fields and esoteric concepts.

Knowing that many of the uses of the terms are related to selling fraudulent products or unprovable concepts, it becomes easier to spot them when they’re misused, and to appreciate them when they’re used correctly.

Originally posted here:

Four of the Most Misused Terms in Alternative Medicine – ATTN:

Yale University, Cambridge scientists discover process they hope will lead to cure for MS – West Hartford News

NEW HAVEN >> Scientists from Yale University and the University of Cambridge in England have teamed up to develop a potential cure for multiple sclerosis.

Its the first treatment that addresses the disease by disarming the immune cells that have turned against the bodys nerve cells, rather than simply suppressing them. An autoimmune disease, MS begins when parts of the bodys immune system, rather than fighting off disease, begin to attack healthy cells.

Su Metcalfe, senior research associate in the University of Cambridge Clinical School, discovered the molecular process that stops the attack on the protective myelin sheath around nerves in the brain and central nervous system. Its that destruction of myelin that causes MS.

Tarek Fahmy, associate professor of biomedical engineering and of immunobiology in the Yale School of Engineering and Applied Science, created the delivery system that brings Metcalfes treatment to the site of the disease.

Multiple sclerosis is a devastating disease that can attack people as young as 30, slowly reducing their brain volume, Metcalfe said. Theyre looking forward to 40 years of slowly getting worse, she said. Its a horrible disease and it costs the global economy $100 billion a year.

According to the National Multiple Sclerosis Society, there are more than 2.3 million cases worldwide, but the society doesnt provide an estimate of U.S. cases because doctors are not required to report new cases. There are a wide variety of symptoms, including fatigue, numbness and tingling muscles, slurred speech, walking difficulties and muscle spasms.

Among the cells in the immune system are T lymphocytes, or T cells. One of their functions is to produce molecules called cytokines, which specialize in alerting immune system cells to infection, cancer or any foreign intrusion in the body, Fahmy said. The immune cells then rush to the site to fight the disease, he said.

However, T cells can go awry and turn from fighting disease to attacking the bodys own cells. In these disease states the T cells make an error whose root cause is still an enigma to scientists and clinicians, Fahmy said. If this happens, then these malfunctioned T cells will produce cytokines that bring in more T cells to the site and the illness cascade of events begins.

He said the same process also is involved in other autoimmune diseases, such as type 1 diabetes and lupus.

Metcalfe said that in 2005 she discovered that another cytokine, called leukemia inhibitory factor, or LIF, regulates the immune response to stop autoimmune attack. The molecule controls a switch that turns the T cells from destroyers to protectors. The way LIF acts on T cells was a critical discovery, she said.

That was a world first, and we discovered that theres a binary switch in the cell so the cell can either become tolerant or aggressive and that switch is operated by LIF, Metcalfe said.

LIF comes in and cuts off the signal that calls in more T cells, Fahmy said.

The challenge to getting LIF to the diseased site was that it is a short-lived molecule. It breaks down within 20 minutes, Metcalfe said. So a way had to be found to deliver it to the T cells. Thats where Fahmys engineering expertise came in.

Fahmy confronted two issues in addition to LIFs delicate nature. One is to avoid having LIF turn off the immune properties of cells throughout the body, the way chemotherapy attacks both healthy and cancerous cells. It has to be targeted to those areas and it has to be a long-lasting signal as well, Fahmy said.

A third factor is we need a high concentration of LIF in that area, he said. The question then becomes, how do you get a high amount of nullifying molecules to the area thats affected and to have those LIF molecules sustained over a long period of time.

Fahmys solution was to create a nanoparticle, one ten-thousandth the width of a human hair follicle (100 to 200 nanometers), which carries the LIF molecules to the T cell like a truck carrying cargo. He used the same material used in soluble stitches and coated it with a protein that only binds to those immune cells that are attacking the rogue T cells. Then, the nanoparticle was loaded with LIF molecules and freeze-dried.

When theyre exposed to water again, they start degrading and as they degrade they release the LIF, Fahmy said. So its like a new drug, except its using older materials, combining them together. Im very hopeful that this is going to work like how natural processes in the body work.

Fahmy said the nanoparticle delivery method is important because, given alone by itself, this drug LIF is a very toxic drug if administered to people without a delivery apparatus. Using the nanoparticle, the amount of LIF that needs to be delivered is 10,000-fold lower than if it were given directly.

Metcalfe and Fahmy have formed a company called LIFNano, which will bring their treatment to clinical trials by 2020. Im committed, Metcalfe said. Ive given my whole career, switched it over to treat patients.

Ive just received 1 million pounds from the U.K. government to do pre-clinical, pre-regulatory work. Part of that million pounds is going to Yale. So Yale remains very closely involved alongside and were continuing this synergistic value in taking this nano-medicine approach to treat patients, she said.

Metcalfe and Fahmy hope their therapy, treating the cells with a naturally occurring molecule, will eventually replace the standard treatment of giving immune-suppressant drugs, which carry their own risks.

This really is a whole new field of study that we call immune-engineering, and it promises to change how therapy will happen for cancer and autoimmune diseases, Fahmy said.

Theres nothing specific controlling the root cause of disease, which is what were doing, and in addition were repairing the myelin and protecting the nerves and theres nothing out there today that protects the nerves, Metcalfe said.

She said she has been at Cambridge her whole career and working to understand what controls lymphocytes and I found LIF. Its been a long journey.

Call Ed Stannard at 203-680-9382.

Link:

Yale University, Cambridge scientists discover process they hope will lead to cure for MS – West Hartford News

Researchers target gene to treat inflammatory bowel disease – Medical Xpress

June 21, 2017 by Becky Freemal Treatments targeting a gene known as NLRX1 could help provide relief to the estimated 1.6 million Americans currently suffering from inflammatory bowel disease. Credit: Virginia Tech

Researchers at the Biocomplexity Institute of Virginia Tech have discovered a new therapeutic target for inflammatory bowel diseaseand it’s right inside our immune cells.

The research at the Nutritional Immunology and Molecular Medicine Laboratory (NIMML), at the Biocomplexity Institute of Virginia Tech, targeted the gene known as NLRX1 as one that has potential therapeutic effects to aid in the treatment of gastrointestinal inflammation.

This investigation into how immunology and metabolism interface may hold critical answers for next generation nutritional immunology. The findings from the team’s most recent research were published in the Journal of Immunology.

It’s this sort of discovery that has the potential to customize healthcare for the individual, from personalized nutrition to precision medicine. The team uncovered new mechanistic insights into the role of NLRX1, targeting cellular metabolism and offering new therapeutic possibilities beyond traditional targets in autoimmune disease treatment.

“For decades, immunologists have applied reductionist approaches to studying the smallest details of the immune response without considering crucial system-wide interactions with nutrition and metabolism,” said Josep Bassaganya-Riera, director of NIMML, a professor of immunology, and CEO of BioTherapeutics. “Our laboratory has built predictive computational and mathematical models and artificial intelligence pipelines capable of analyzing complex, massively interacting systems, including interactions between immunity and metabolism. This study not only elucidates novel mechanisms of immunoregulation in IBD, but it also validates transcriptomic and computational modeling studies that predicted the importance of NLRX1 in regulating gastrointestinal inflammation and its potential as a therapeutic target for infectious and immune-mediated diseases.”

Due to an incomplete understanding of how NLRX1 works to decrease inflammation, scientific attempts to target this molecule as a treatment for the disease had previously stalled. The lab team’s findings provide a deeper understanding of this gene’s role in mucosal immunity and metabolism. This levels the playing field for both nutritional interventions that target NLRX1 and the development of NLRX1-based drugs.

“This seminal work, while impactful independently, sets the stage for the next lines of applied investigation on the role of NLRX1 in IBD,” said Andrew Leber, scientific director of BioTherapeutics. “It highlights the need to understand not only the immediately relevant pathways for novel immunoregulatory genes, but their global effect on all of the cohesive metabolic and immunological processes within a cell, a goal that we will continue to pursue.”

This work builds upon NIMML’s successful track record in leading innovative transdisciplinary research at the interface of nutrition, immunity, and metabolism that dates back to its founding in 2002. The NIMML team has been involved in establishing spinoff companies that translate new scientific discoveries into the development of marketable products that address unmet consumer or clinical needs.

Explore further: Solving the immunity puzzle takes collaboration among different fields

More information: Andrew Leber et al. NLRX1 Regulates Effector and Metabolic Functions of CD4T Cells, The Journal of Immunology (2017). DOI: 10.4049/jimmunol.1601547

Studying the human immune system is like trying to work a vast, multidimensional jigsaw puzzle with pieces that are constantly changing shape. Billions of microbes interact with the host, shaping the processes that keep us …

UNC Lineberger Comprehensive Cancer Center researchers have discovered that a deficiency in a key protein that regulates immune system warning signals could be a new biomarker for colorectal cancer, the second largest cancer …

Scientists at the University of North Carolina (UNC) School of Medicine and Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a human (host) protein that weakens the immune response to HIV and other …

The human immune system is a double-edged sword. While it is finely adapted to fighting potentially deadly viruses, such as the H1N1 influenza, the mechanisms it uses to fight pathogens can have negative effects such …

Building on previous work with the botanical abscisic acida, researchers in the Nutritional Immunology and Molecular Medicine Laboratory (NIMML) have discovered that abscisic acid has anti-inflammatory effects in the lungs …

The Nutritional Immunology and Molecular Medicine Laboratory (NIMML) research team at Virginia Tech has discovered important new information on the efficacy of conjugated linoleic acid (CLA) in treating Crohn’s disease, a …

Scientists from St. Jude Children’s Research Hospital and Fred Hutchinson Cancer Research Center have developed an algorithm that functions like a Rosetta Stone to help decipher how the immune system recognizes and binds …

Researchers at the Biocomplexity Institute of Virginia Tech have discovered a new therapeutic target for inflammatory bowel diseaseand it’s right inside our immune cells.

A subpopulation of immune cells that normally fend off pathogens can turn against the host during certain infections, a new study publishing on June 20 in the open access journal PLOS Biology reveals.

In recent years, immunotherapy, a new form of cancer therapy that rouses the immune system to attack tumor cells, has captivated the public’s imagination. When it works, the results are breathtaking. But more often than not …

Exposure to sunlight releases a compound from the skin that can alleviate symptoms of eczema, research has found.

Racial discrimination experienced by African-American children and young adults exacerbates a type of asthma known to be resistant to standard treatment, according to a study headed by researchers at UC San Francisco.

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Researchers target gene to treat inflammatory bowel disease – Medical Xpress

Yale University, Cambridge scientists discover process they hope will lead to cure for MS – New Haven Register

NEW HAVEN >> Scientists from Yale University and the University of Cambridge in England have teamed up to develop a potential cure for multiple sclerosis.

Its the first treatment that addresses the disease by disarming the immune cells that have turned against the bodys nerve cells, rather than simply suppressing them. An autoimmune disease, MS begins when parts of the bodys immune system, rather than fighting off disease, begin to attack healthy cells.

Su Metcalfe, senior research associate in the University of Cambridge Clinical School, discovered the molecular process that stops the attack on the protective myelin sheath around nerves in the brain and central nervous system. Its that destruction of myelin that causes MS.

Tarek Fahmy, associate professor of biomedical engineering and of immunobiology in the Yale School of Engineering and Applied Science, created the delivery system that brings Metcalfes treatment to the site of the disease.

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Multiple sclerosis is a devastating disease that can attack people as young as 30, slowly reducing their brain volume, Metcalfe said. Theyre looking forward to 40 years of slowly getting worse, she said. Its a horrible disease and it costs the global economy $100 billion a year.

According to the National Multiple Sclerosis Society, there are more than 2.3 million cases worldwide, but the society doesnt provide an estimate of U.S. cases because doctors are not required to report new cases. There are a wide variety of symptoms, including fatigue, numbness and tingling muscles, slurred speech, walking difficulties and muscle spasms.

Among the cells in the immune system are T lymphocytes, or T cells. One of their functions is to produce molecules called cytokines, which specialize in alerting immune system cells to infection, cancer or any foreign intrusion in the body, Fahmy said. The immune cells then rush to the site to fight the disease, he said.

However, T cells can go awry and turn from fighting disease to attacking the bodys own cells. In these disease states the T cells make an error whose root cause is still an enigma to scientists and clinicians, Fahmy said. If this happens, then these malfunctioned T cells will produce cytokines that bring in more T cells to the site and the illness cascade of events begins.

He said the same process also is involved in other autoimmune diseases, such as type 1 diabetes and lupus.

Metcalfe said that in 2005 she discovered that another cytokine, called leukemia inhibitory factor, or LIF, regulates the immune response to stop autoimmune attack. The molecule controls a switch that turns the T cells from destroyers to protectors. The way LIF acts on T cells was a critical discovery, she said.

That was a world first, and we discovered that theres a binary switch in the cell so the cell can either become tolerant or aggressive and that switch is operated by LIF, Metcalfe said.

LIF comes in and cuts off the signal that calls in more T cells, Fahmy said.

The challenge to getting LIF to the diseased site was that it is a short-lived molecule. It breaks down within 20 minutes, Metcalfe said. So a way had to be found to deliver it to the T cells. Thats where Fahmys engineering expertise came in.

Fahmy confronted two issues in addition to LIFs delicate nature. One is to avoid having LIF turn off the immune properties of cells throughout the body, the way chemotherapy attacks both healthy and cancerous cells. It has to be targeted to those areas and it has to be a long-lasting signal as well, Fahmy said.

A third factor is we need a high concentration of LIF in that area, he said. The question then becomes, how do you get a high amount of nullifying molecules to the area thats affected and to have those LIF molecules sustained over a long period of time.

Fahmys solution was to create a nanoparticle, one ten-thousandth the width of a human hair follicle (100 to 200 nanometers), which carries the LIF molecules to the T cell like a truck carrying cargo. He used the same material used in soluble stitches and coated it with a protein that only binds to those immune cells that are attacking the rogue T cells. Then, the nanoparticle was loaded with LIF molecules and freeze-dried.

When theyre exposed to water again, they start degrading and as they degrade they release the LIF, Fahmy said. So its like a new drug, except its using older materials, combining them together. Im very hopeful that this is going to work like how natural processes in the body work.

Fahmy said the nanoparticle delivery method is important because, given alone by itself, this drug LIF is a very toxic drug if administered to people without a delivery apparatus. Using the nanoparticle, the amount of LIF that needs to be delivered is 10,000-fold lower than if it were given directly.

Metcalfe and Fahmy have formed a company called LIFNano, which will bring their treatment to clinical trials by 2020. Im committed, Metcalfe said. Ive given my whole career, switched it over to treat patients.

Ive just received 1 million pounds from the U.K. government to do pre-clinical, pre-regulatory work. Part of that million pounds is going to Yale. So Yale remains very closely involved alongside and were continuing this synergistic value in taking this nano-medicine approach to treat patients, she said.

Metcalfe and Fahmy hope their therapy, treating the cells with a naturally occurring molecule, will eventually replace the standard treatment of giving immune-suppressant drugs, which carry their own risks.

This really is a whole new field of study that we call immune-engineering, and it promises to change how therapy will happen for cancer and autoimmune diseases, Fahmy said.

Theres nothing specific controlling the root cause of disease, which is what were doing, and in addition were repairing the myelin and protecting the nerves and theres nothing out there today that protects the nerves, Metcalfe said.

She said she has been at Cambridge her whole career and working to understand what controls lymphocytes and I found LIF. Its been a long journey.

Call Ed Stannard at 203-680-9382.

Read the original:

Yale University, Cambridge scientists discover process they hope will lead to cure for MS – New Haven Register

Mesothelioma Clinical Trial Opens with High Expectations – Asbestos.com

Newly diagnosed mesothelioma patients around the world have begun enrolling in a much-anticipated, phase III clinical trial involving an immunotherapy drug combination with groundbreaking potential.

The trial, designed as first-line therapy for unresectable pleural mesothelioma, will measure the effectiveness of nivolumab (Opdivo) and ipilimumab (Yervoy) against standard-of-care chemotherapy.

A presentation this month at the 2017 American Society of Clinical Oncology (ASCO) annual meeting sparked high expectations for the trial, detailing early, impressive effectiveness involving the two drugs in second-line and third-line treatments.

Pharmaceutical giant Bristol-Myers Squibb is sponsoring the latest clinical trial that will include investigational sites in 20 countries and 17 cancer centers across the U.S., including:

Were ultimately hoping [with this trial] to forge a new standard of care for mesothelioma, Dr. Patrick Ma, lead investigator at WVU Cancer Center, told Asbestos.com. Yes, the expectations for this trial are high.

The ASCO presentation in Chicago was based on a multi-center phase II trial in France that included 125 patients with recurrent mesothelioma and measured the effectiveness of nivolumab against a nivolumab and ipilimumab combination.

The disease control rate (DCR) the percentage of patients in which the cancer either does not grow or shrinks was 50 percent at the 12-week mark for those getting the drug combination.

It was 44 percent for those receiving only nivolumab. According to the investigators, previous studies using other second-line treatments managed only a 30 percent DCR.

Tumors shrank in 26 percent of patients getting both drugs and in 17 percent of those receiving just the one. The median progression-free survival (until the cancer worsens) was 5.6 months with the combination and four months with the single drug.

Severe side effects were more common with the drug combination than with nivolumab alone, with 18 percent and 10 percent of patients reporting, respectively.

Our findings suggest that immunotherapy may provide new hope to patients with relapsed mesothelioma, said lead study author Dr. Arnaud Scherpereel of University Hospital of Lille in France. It is too early to conclude whether nivolumab alone or the combination is better.

The phase III trial, which is preparing for 600 participants across the 20 countries, is expected to last until 2021. Newly diagnosed patients with unresectable disease are encouraged to participate.

It is a randomized trial in which the immunotherapy drug combination will be measured against a pemetrexed and cisplatin or carboplatin chemotherapy combination.

The concept of clinical trials needs to be promoted for mesothelioma patients, whose standard of care has been chemotherapy after chemotherapy that has not produced a wonderful response or a satisfactory outcome, Ma said. In a sense, these trials should be seen as just part of modern clinical care.

Unlike chemotherapy, immunotherapy drugs are designed to boost the bodys natural defenses to fight the cancer. They work by blocking the molecules which prevent the immune system from recognizing the cancer as foreign.

Ma, co-leader of the lung cancer program at WVU, believes immunotherapy is the future for many tough-to-treat cancers, including mesothelioma.

In 2015, nivolumab was the first immunotherapy drug approved by the U.S. Food & Drug Administration (FDA) for non-small cell lung cancer as a second-line treatment.

In May, the FDA approved pembrolizumab (Keytruda) in combination with chemotherapy for first-line treatment of non-small cell lung cancer, another first for an immunotherapy drug.

Pharmaceutical company Merck is expected to announce soon its latest mesothelioma clinical trial involving a combination of Keytruda and CRS-207, a drug form of the Listeria bacteria.

More immunotherapy combination trials are on the horizon for many cancers.

We are only at the dawn of the immunotherapy revolution. We are moving inch-by-inch closer to better treatment for these cancers, Ma said. In the big picture of things, there is still so much more we can learn about the immune system that will lead to significant advancements.

Mesothelioma, which has no definitive cure, is an aggressive cancer typically caused by occupational exposure to asbestos. The FDA has not approved a new treatment for first line mesothelioma therapy since 2005.

The majority of patients with pleural mesothelioma live less than 18 months after diagnosis.

People need to pay more attention to this rare disease, Ma said of mesothelioma. It is really emotional walking with them through this [cancer] journey and not having great treatment options. Hopefully now, were closer to finding a better way to treat them.

Read more:

Mesothelioma Clinical Trial Opens with High Expectations – Asbestos.com

The Challenges of Research in Immunotherapy – Mesothelioma.com (blog)

Cancer research has made great advancements in recent years with emerging treatments like immunotherapy. Harnessing the immune system in different ways to better combat cancer has proven effective for a variety of cancer types, including mesothelioma. But there is still a lot of work ahead to truly understand how the treatment can be most effective.

While this progress with immunotherapy has given patients a lot of hope, it hasnt been an easy road and there are still many obstacles to face before the treatment reaches its full potential. Researchers have already faced many barriers with clinical trials and the cost of this treatment, and there will likely only be more challenges ahead.

In observance of Cancer Immunotherapy Month, we spoke with medical professionals working in different specialties to get their take on immunotherapy. In the first article of this series, we asked them about the potential for immunotherapy and recent exciting developments. In this article, we learned what barriers theyve come up against and potential future obstacles for the emerging treatment.

In many cases, patients can only receive immunotherapies through clinical trials because the treatment is still so new. Researching a new drug or type of treatment takes years, and the process goes through different phases of testing. It can be a delicate balance of finding the right clinical trial at the right time during its different phases of research.

There are thousands of clinical trials going on at any given time, and it can be difficult to understand all the nuances of choosing and joining a clinical trial. Its understandably an overwhelming decision to choose a clinical trial to pursue from a list of possibly hundreds a patient may be eligible for. Even with advice from an oncologist and lots of research, patients may be taking a gamble on choosing one promising clinical trial over another.

Research shows, however, that many patients dont even consider such a decision. The majority of cancer patients choose not to participate in a clinical trial and stick with standard treatment methods instead.

There are so many clinical trials that need to be done to get us to the next steps. Clinical trials are, for the most part, the best therapy available to patients, explained Dr. Ezra Cohen, the director of translational science at UC San Diego. The sobering reality is that only 3% of adult cancer patients participate in clinical trials. We need to urgently break down barriers to participation and encourage patients to seek out clinical trials.

For those that do choose to participate, there are no guarantees. Different phases of clinical trials take on varying numbers of participants, which ultimately puts some patients on a waiting list to see if they can have their chance at a promising new treatment. And even if the patients are able to join and begin the trial, there are never any guarantees the treatment will work for them or what kind of side effects they may experience.

But despite the risks involved, researchers hope patients take the time to learn about clinical trials they may be eligible for and take a leap of faith. I encourage all eligible patients to consider clinical trials, especially when immunotherapy agents are involved, because it is through these trials that we develop the science and improve patient outcomes, insisted Dr. Bradley Corr, assistant professor in gynecologic oncology at the University of Colorado.

The research is still expensive but I believe more critical now than ever. We are at a time when the technology, biology, and drug development have come together in a way that will change the field forever. We must take advantage of that, said Dr. Cohen.

Cancer treatment costs in general have grown exponentially over the years with no sign of lowering any time soon. The cost of making a cancer drug and going through these trials can be well over a billion dollars, and unfortunately leads to patients also taking on a high expense to receive the treatment.

Keytruda (pembrolizumab) for instance has shown promise for mesothelioma and other cancers, but the cost of the drug can be well beyond many patients means. Recent estimates say Keytruda costs about $13,000 every month, which would add up to $156,000 for one year of treatment.

Once you get to the third, fourth or ninth treatment, you have incurred a lot of treatment cost, and if you dont have coverage what do you do? said Dr. Satish Shah, an oncologist and hematologist at Gettysburg Cancer Center. How can you not have treatment that is potentially life saving? [But] if one treatment is $10,000, how can you justify that treatment?

Since these drugs are often part of clinical trials, much of these costs will be covered by the sponsor of the study. However, that doesnt mean the participants wont have any costs of their own. Any additional testing or procedures required as a result of the trial often arent covered by insurance, though in some cases the sponsor will also cover these additional expenses.

But even with coverage, health insurance is often not enough when dealing with cancer, and its estimated patients on average pay at least 20 30% of cancer drugs costs out of their own pockets. Many cancer treatments and clinical trials span well beyond a single calendar year, meaning patients often end up with a lifetime of debt to receive lifesaving treatment.

Whether participating in a clinical trial or turning to more conventional treatments, patients face a hefty price tag. Chemotherapy, for example, costs a few thousand dollars for a single treatment, so one round of chemo can reach upwards of $50,000.

Though there are some options to alleviate the financial burden of cancer treatment, the price of these drugs can often cause patients to avoid the potential benefits of a more costly emerging treatment.

Since immunotherapies are still in the early developmental stages, researchers still have a lot to learn. As with any developing treatment, there are still many unknowns and more questions will likely continue to emerge as research continues.

I think the biggest barrier presently is our need to understand the immune system further and execute the experiments that move the field forward, said Dr. Cohen.

The immune system is extremely complex, and will take time for researchers to fully understand how it reacts with these new treatments, as well as how cancer reacts with our immune system. One main focus of research currently is determining why immunotherapy has worked so well in certain types of cancers, but not in others, which researchers believe is because of the immune environment. Researchers also question the side effects patients may encounter.

This particular type of treatment is very different so one challenge would be familiarity with the administration of these drugs to understanding the side effects and appropriately because some of these side effects could be permanent damage, Dr. Shah explained. So you have to be knowing as a health care provider, and you as a patient, what changes have occurred and be careful what you report to your doctor so your doctor is aware of what to look for.

Immunotherapies have been found to cause a wide range of side effects, such as skin reactions or flu-like symptoms. In general, researchers have said these therapies are pretty well tolerated, but there are a lot of unknowns in terms of how immunotherapy might affect the body over a long period of time or years after treatment.

Regardless of the obstacles and risks, immunotherapy is an exciting new treatment that has the potential to change cancer care for good. With continued research and support, it will likely only become more effective for more cancers, and maybe even help lead to a cure.

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The Challenges of Research in Immunotherapy – Mesothelioma.com (blog)

Newly Designed Viral Vectors Could Lead to Improved Gene Therapies – Bioscience Technology

For many patients, participating in gene therapy clinical trials isnt an option because their immune system recognizes and fights the helpful virus used for treatment. Now, University of Florida Health and University of North Carolina researchers have found a solution that may allow viruses used for gene therapy to evade the bodys normal immune response.

The discovery, published in the Proceedings of the National Academy of Sciences, is a crucial step in averting the immune response that prevents many people from taking part in clinical trials for various disorders, according to co-author Mavis Agbandje-McKenna, Ph.D., a professor in the University of Florida College of Medicine department of biochemistry and molecular biology and director of the Center for Structural Biology.

During gene therapy, engineered viruses are used to deliver new genes to a patients cells. While the recombinant adeno-associated virus, or AAV, is effective at delivering its genetic cargo, prior natural exposure to AAV results in antibodies in some people. As many as 70 percent of patients have pre-existing immunity that makes them ineligible for gene therapy clinical trials, Agbandje-McKenna said.

The findings provide a road map for designing virus strains that can evade neutralizing antibodies, said Aravind Asokan, PhD, an associate professor in the department of genetics at the University of North Carolina School of Medicine, who led the study.

University of Florida first identified the structural footprints where pre-existing antibodies interact with the virus, using an cryo-electron microscope. The UNC researchers then evolved new viral protein shells. Using serum from mice, rhesus monkeys, and humans, the researchers showed that the redesigned virus can slip past the immune system.

This is the blueprint for producing AAV strains that could help more patients become eligible for human gene therapy. Now we know how to do it, Agbandje-McKenna said.

While the findings prove that one variation of AAV can be evolved, further study in preclinical models is needed before the approach can be tested in humans. Next, the immune profile of one particularly promising virus variant will need to be evaluated in a larger number of human serum samples, and dose-finding studies are needed in certain animal models. Researchers may also need to study whether the same virus-manipulating technique can be used in a broader range of gene therapy viruses, Agbandje-McKenna said.

Although human gene therapy remains an emerging field and has yet to reach patients on a wide scale, researchers elsewhere have used AAV therapy to successfully treat hemophilia, a blood-clotting disorder, in a small trial. It has also been or is now being studied as a way to treat hereditary blindness, certain immune deficiencies, neurological and metabolic disorders, and certain cancers.

The latest findings are the result of more than 10 years of studying the interactions between viruses and antibodies and a long-standing collaboration with Asokan, who heads the synthetic virology group at the UNC Gene Therapy Center.

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Newly Designed Viral Vectors Could Lead to Improved Gene Therapies – Bioscience Technology

The Importance of Cancer Research in Immunotherapy – Mesothelioma.com (blog)

Our immune system is a powerhouse that works hard constantly to protect the body from disease. In a fight against cancer, researchers have found great potential in harnessing and boosting the efforts of the immune system to attack the cancer cells. This treatment, known as immunotherapy, is still developing but has shown promise for a number of cancers already.

For patients with rare cancers such as mesothelioma, immunotherapy can provide hope in the face of such a dire prognosis. Mesothelioma often isnt properly diagnosed until it has developed to a later stage with fewer treatment options. Some patients have seen success with immunotherapy and credit the treatment for giving them their life back. Keytruda, in particular, has shown promise for some patients and has helped them live beyond the typical 12 21 months.

This June marks the 5th annual Cancer Immunotherapy Month, which celebrates the lifesaving potential of immunotherapies. In honor of this month, we reached out to medical professionals in various fields to hear their opinions on the emerging treatment and what lies ahead.

Immunotherapy works by either stimulating the bodys immune system to work smarter and attack the cancer cells, or by introducing man-made immune proteins to fight the cancer cells, such as monoclonal antibodies. There are many kinds of immunotherapy, though the majority of these therapies are only currently available through clinical trials.

So far, immunotherapy has typically been used as a stand-alone treatment or in combination with surgery. Some researchers believe with further study, immunotherapy could one day replace the more conventional treatments, like chemotherapy and surgery.

I think we will learn how to combine immunotherapy with conventional treatment first but eventually, as we develop immunotherapy options and understand which patients benefit from which drugs, we will begin to replace existing treatments, Dr. Ezra Cohen, the translational science director at UC San Diego, recently told the Mesothelioma Cancer Alliance.

Other researchers believe immunotherapy will likely be utilized in combination with the typical cancer treatments. For many cancer patients, a multimodal treatment approach has proven more effective than a singular treatment.

Immunotherapy is a phenomenal new tool in our armament of treatment options for patients. However, it is certainly in its developmental stages in most cancers, said Dr. Bradley Corr, assistant professor on the gynecologic oncology team at the University of Colorado. The way I see the research going and potential for its use is more as an addition to rather than a replacement for conventional treatment options.

In some cases, immunotherapy has already been seen as an almost miraculous treatment. Mesothelioma patient Mavis Nye was first diagnosed in 2009, and today is in remission after joining an immunotherapy clinical trial. After four years of standard chemotherapy, Mavis was basically out of options.

On her deathbed, she was finally able to participate in a clinical trial studying Keytruda, a monoclonal antibody drug that works by targeting proteins in cancer cells and disrupting their growth. After two years on the trial, Maviss tumors continued to shrink into obscurity. Her success with the drug has given other mesothelioma patients hope. Keytruda has also shown promise for melanoma, non-small cell lung cancer, and head and neck squamous cell carcinoma (HNSCC).

The most exciting thing is watching people who previously were dying of untreatable cancers, like melanoma of the skin, have their tumors melt away during treatment. I think the key word is dramatic; a potentially dramatic benefit as a life changing event, said Dr. Eric Whitman, a surgical oncologist from Atlantic Medical Group who specializes in melanoma.

Learn more about immunotherapy & other emerging mesothelioma treatments

While immunotherapy has proven to be effective for a number of cancers, there are still many types that have yet to see success with this new treatment. Because of the success weve seen for immunotherapy in immune responsive cancers such as melanoma, the initial outlook towards its use in other malignancies was high, explained Dr. Corr. Unfortunately, we havent seen similar response rates in all cancer types across the board.

Researchers are working to better understand how the immune system works and why certain cancers are not seeing such positive responses to this treatment. There are hundreds of kinds of cancer, and even similar diagnoses wont be exactly the same, adding to the difficulties they face in their studies.

We are just starting to understand why some types of cancers seem more likely to respond to currently available immunotherapy, Dr. Whitman explained. It appears that the difference may not entirely be the cancers themselves, but the environment and architecture of the tumor as it grows, which may make it relatively harder or easier for immunotherapy drugs, and of course the immune system itself, to effectively attack the cancer.

Others are developing new approaches for its use. As mentioned, immunotherapy has often been used on its own or as a post-surgical treatment. An ongoing mesothelioma clinical trial at Baylor University is among the first studying the effectiveness of immunotherapy before surgery. The trial is testing variations with checkpoint inhibitors and studying the immune responses of the patients tumors.

Though its still early, initial findings have shown promise for effective long-term results. The trials lead researcher, Dr. Burt, believes immunotherapy will become a critical component in multimodal treatment for mesothelioma and possibly other cancers as well.

As these current trials progress and new studies emerge, the possibilities for immunotherapy will likely continue to grow with more understanding.

As much success as we have seen, we are still really in the beginning stages of understanding the complexities of the interaction between cancers and our immune systems, Dr. Whitman insisted. I expect our understanding of this interaction to grow by several quantum leaps over the next few years.

Research like this is our greatest asset in the fight to end cancer once and for all. These emerging treatment methods have the potential to transform the standard for cancer care, and bring us closer to a possible cure for even rare cancers like mesothelioma.

Support for these studies through better awareness, increased funding, and continued participation from eligible patients is critical. This research has already positively influenced many patients and their families, and one day could possibly eliminate cancer for all.

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The Importance of Cancer Research in Immunotherapy – Mesothelioma.com (blog)

Column: Stem Cell Therapy A medical revolution – Current in Carmel

Commentary by Dmitry M. Arbuck, MD, President and Medical Director, Indiana Polyclinic

We are at a truly revolutionary time in health and medicine. The introduction of stem cell technology represents innovation on the same level as the development of antibiotics or the invention of modern imaging (MRIs, etc.). Stem cells are already changing the way medicine is delivered, increasing lifespans and saving countless lives.

Arbuck

Scientists and researchers have been studying the benefits of stem cells for more than 30 years. They have found that these special cells provide great benefits all over the body, from muscles and joints to chronic diseases, to growing new teeth. You may have read about athletes treated with stem cells to speed healing after an injury or about burn victims who use stem cell therapy to minimize scarring.

Stem cells used to be associated with embryos, but this is no longer the case. Today, live cells for treatment are either adult stem cells or umbilical cord blood stem cells. Adult stem cells are most likely extracted from tissue, like bone marrow or fat, which can be a painful and invasive process. Additionally, as we age, so do our stem cells, which become less potent and productive over time. Like every other tissue in our bodies, they are exposed to the toxins, radiation and other pollutants in the environment. Umbilical cord blood stem cells are collected from the donated cord blood and placenta of healthy newborns. The cells are then screened for disease and genetic problems. These umbilical stem cells are vibrant, vital and healthy.

When umbilical cord stem cells are infused, they carry a whole host of immune stabilizing factors throughout the body and work to repair the immune system. This is likely why stem cells are so helpful in the treatment of autoimmune diseases such as rheumatoid arthritis, Crohns disease, dermatitis and myasthenia gravis. Other things that may be successfully treated with this therapy include MS, lupus, graft vs. host disease and other immune conditions.

The future is today. For more, visit StemCellsIndy.com.

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Column: Stem Cell Therapy A medical revolution – Current in Carmel

Allergy treatment: Scientists claim breakthrough that could lead to … – The Independent

Scientists in Australia claim to have discovered what could be a life-long cure for potentially fatal allergies to peanuts, shellfish and other food.

The researchers said they had been able to turn off the allergic response in tests on mice using gene therapy to desensitise the bodys immune system, and suggested this could also be used to treat asthma.

They predicted human trials could begin in just five or six years.

Commenting on the study, a leading British expert said scientists had managed to cure allergies in mice before without this leading to an effective human treatment, but added that the new research could lead to the “Holy Grail” of allergy treatment.

He was sceptical about the researchers’ claims their technique might be effective against asthma, but Asthma UK said it was “a very exciting step forward”.

Allergies occur when the immune system over-reacts to something that is usually harmless. In the journal JCI Insight, the Australian researchers reported they had used genetic techniques to prevent this from happening in mice who were allergic to the protein in egg whites.

In a video about the new research, Professor Ray Steptoe, of Queensland University, said: We can actually turn off the response. What that means is the disease is stopped in its tracks.

What we do is we stop the underlying disease that causes these symptoms. That could revolutionise treatment for severe allergies. It would prevent, we think, some of the life-threatening allergic episodes that occur for people who are allergic to foods for instance.

That would make a huge difference for people with severe allergies what that would mean is they would no longer be in fear of life-threatening incidents if they were to go to a restaurant and be exposed to shellfish and they werent aware that was in the food.

Kids with peanut allergies could go to school without any fear of being contaminated from other kids food.

We envisage in the future, with this approach, that they could go to the doctors rooms, get a single treatment and that would give them permanent protection from future allergic attacks or asthma attacks.

He added that the researchers hoped human trials could begin in five to six years, estimated it would take a similar period after that for the treatment to be available to patients.

Professor Adnan Custovic, an allergy expert at Imperial College London, expressed particular caution about the claim the treatment would be effective against asthma as the condition is caused by a completely different mechanism to the one behind food allergies.

But he added: This is one of the potentially exciting approaches to treating allergies.

Its sort of approach, where you try to switch off the allergic response, is kind of the Holy Grail, but a mouse model is not the same as a human model.

We can cure allergies in mice but we cannot do it in humans the mechanisms are not identical. Only time will tell whether this approach will be a viable one.

And he criticised the degree of optimism about the technique expressed by the Australian team.

My real problem with this sort of bombastic statements like this is people with asthma it gives them hope which very often is not realistic, Professor Custovic said.

However Dr Erika Kennington, head of research at Asthma UK, was more optimistic.

This is potentially a very exciting step forward in asthma research,” she said.

“Allergen immunotherapy exposing people to small amounts of an allergen in order to build up tolerance is currently the only disease-altering treatment available for asthma but it can have significant side effects in some people, and every other existing asthma treatment and medication works by reducing or relieving the symptoms.

“These findings suggesting a novel approach to reversing allergic disease are therefore very welcome.

We also know that there are certain allergy triggers that cause asthma flare ups, which makes this research important in possibly reducing the risk of life-threatening asthma attacks.”

But Dr Kennington also pointed to the difference between animal and human trials.

A lot more research is needed to see if the same results can be achieved in people before we can say that a cure for asthma is around the corner,” she said.

In the study of the allergic mice, the researchers inserted a gene into blood stem cells that controls the immune response to the egg white.

The genetically modified cells were then injected into the mices bone marrow, where they produced new blood cells that were able to turn off the allergic response.

The researchers hope to create a similar form of gene therapy that works on humans after a single injection.

We havent quite got it to the point where its as simple as getting a flu jab, so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals, Dr Steptoe said.

Dr Louisa James, British Society for Immunology spokesperson and an immunologistat Queen Mary University of London, said allergies were “far more complex than can be replicated in an animal model”.

“Patients with severe allergies often react to several different types of allergen and symptoms can develop over several years,” she said.

“Although the results are encouraging and heading in the right direction, it is too early to predict whether this form of therapy could ever be used to treat allergies in humans.

“As the authors state in their paper ‘gene-therapy is not yet suitable for clinical application to mild disease in young individuals’.

“There are simply too many open questions around the translation of these findings from animal models into humans.Would the cells engineered to produce allergens produce the same response in humans? How would other immune cells that play a critical role in human allergy be affected? What are the mechanisms that switch off the immune response and are they comparable in humans?

This approach holds promise, and further research is certainly warranted, but claims that a single injection could switch off allergies are over-optimistic at this time.

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Allergy treatment: Scientists claim breakthrough that could lead to … – The Independent

Early research suggests first immunotherapy for mesothelioma on the horizon – Medical Xpress

June 5, 2017

Malignant pleural mesothelioma or MPM is a rare cancer, but its incidence has been rising. This cancer is usually associated with asbestos exposure, and patients have a median life expectancy of only 13-15 months. All patients relapse despite initial chemotherapy, more than 50% of them within six months after stopping treatment. There are currently no effective therapeutic options for patients with MPM.

Early findings from an ongoing phase II clinical trial in France, MAPS-2, show that immunotherapy may slow the growth of MPM after relapse. At 12 weeks, cancer had not worsened in 44% of patients who received nivolumab (Opdivo) and in 50% of those who received nivolumab with ipilimumab (Yervoy).

The study will be featured in a press briefing today and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Our findings suggest that immunotherapy may provide new hope to patients with relapsed mesothelioma,” said lead study author Arnaud Scherpereel, MD, PhD, head of the Pulmonary and Thoracic Oncology Department at the University Hospital (CHU) of Lille in Lille, France. “This randomized phase II trial may be enough to support the use of immune checkpoint inhibitors in this setting, but it is too early to conclude whether nivolumab alone or the combination of nivolumab and ipilimumab is better.”

About the Study

This multi-center clinical trial enrolled 125 patients with advanced MPM who had received up to two prior treatments, including standard platinum-based chemotherapy. The majority of patients (80%) were male, and the median age was 72 years. The patients were randomly assigned to treatment with nivolumab alone or nivolumab with ipilimumab until the cancer worsened; 70% of patients received at least 3 cycles of either treatment.

Key Findings

The authors report results from the first 108 patients treated on the study. The disease control rate or DCR, defined as the percentage of patients in which cancer either shrank or did not grow, was 44% among the patients who received nivolumab only and 50% among those who received nivolumab with ipilimumab (the 12-week DCR for all treatments previously tested in relapsed MPM was less than 30%). Tumors shrank in 17% of patients treated with nivolumab and 26% of those treated with nivolumab and ipilimumab.

After a mean follow-up of 10.4 months of the 125 patients, the median time until the cancer worsened (progression-free survival) was 4 months with nivolumab alone and 5.6 months with nivolumab and ipilimumab. The median overall survival was 10.4 months in the nivolumab group and not reached in the nivolumab with ipilimumab group (meaning that more than 50% were still alive at analysis). Mature quality-of-life data are not yet available.

The side effects were rather mild overall with the most common being thyroid problems, colon inflammation, and skin rash. Severe side effects were more common in the nivolumab plus ipilimumab group (18% vs. 10%), in which three treatment-related deaths occurred.

Next Steps

With 125 patients, MAPS-2 is the largest clinical trial of immune checkpoint inhibitors in mesothelioma to date, according to the authors. Many ongoing clinical trials are exploring nivolumab and other immune checkpoint inhibitors as second- or third-line treatments for MPM. In addition, several larger clinical trials investigating immune checkpoint inhibitors as initial therapy for MPM are already under way.

“Mesothelioma cells build a protective tumor microenvironment to shield themselves against the immune system’s attacks and even act against anti-tumor immune response,” said Dr. Scherpereel. “Therefore, therapies that shift the tumor microenvironment from a state of immune suppression to one of immune activation may hold promise in MPM.”

About Mesothelioma

Malignant pleural mesothelioma is a cancer that begins in the lining of the lungs. This cancer is associated with occupational exposure to asbestos, which causes chronic inflammation. It typically takes 30 to 40 years from asbestos exposure to development of MPM.

The peak of asbestos use was between the 1960s and the 1980s. Although use of asbestos has been banned in the United States and many European countries, asbestos is still being used and extracted in many developing countries. “For these reasons, we expect to continue to see growing incidence of mesothelioma in the coming decades,” said Dr. Scherpereel.

Explore further: Immunologic changes point to potential for clinical investigation of combination immunotherapy for deadly kidney cancer

More information: abstracts.asco.org/199/AbstView_199_187024.html

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Early research suggests first immunotherapy for mesothelioma on the horizon – Medical Xpress

A New Gene Therapy Could Hold the Key to Curing Allergies and Asthma – Futurism

In Brief Researchers have successfully used immunotherapy to “turn off” asthma and allergic responses in animals. This work will eventually be used to create one-shot treatments that permanently silence allergies. Erasing Asthma

Scientists from the University of Queensland have used gene therapy to turn off the immune response responsible for asthma. The team believes their technique may also be able to permanently silence severe allergy responses to common allergens such as bee venom, peanuts, and shellfish. Thus far, the research has been successful in animal trials, and if it can be replicated in human trials, it may provide a one-time treatment for asthma and allergy patients.

The technique erases the memory of the cells which cause allergic reactions using genetically modified stem cells that are resistant to allergens. We have now been able wipe the memory of these T-cells in animals with gene therapy, de-sensitizing the immune system so that it tolerates the [allergen] protein, lead researcher Ray Steptoe said in a press release. We take blood stem cells, insert a gene which regulates the allergen protein and we put that into the recipient. Those engineered cells produce new blood cells programmed to express the protein and target specific immune cells, which turn off the allergic response.

According to the Centers for Disease Control (CDC), about 1 in 12 people (25 million) in the U.S.have asthma, and these numbers are increasing annually. As of 2007, the last year for which the CDC has data, asthma cost the U.S. approximately $56 billion in costs for medical bills, lost work and school days, and early deaths. According to the World Health Organization (WHO), 235 million people worldwide have asthma, which is the most common chronic childhood disease, occurring in all countries regardless of level of development.

The researchers findings must now besubjected to further pre-clinical investigation, with the aim of replicating the results in the laboratory using human cells. The longer term goal will be a one-time gene therapy injection that would replace short-term allergy treatments, which vary in their effectiveness. We havent quite got it to the point where its as simple as getting a flu jab so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals, Dr. Steptoe said in the press release.

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A New Gene Therapy Could Hold the Key to Curing Allergies and Asthma – Futurism