Yearly Archives: 2017


Stem Cell Clinic > 2017

Microglia Generation For High-Throughput Experiments Optimized – Technology Networks

By Stell Cell Research

Microglia derived from stem cells. Credit: NYSCF

Scientists from the New York Stem Cell Foundation (NYSCF) Research Institute have developed a robust, efficient method for deriving microglia, the immune cells of the brain, from human stem cells. Microglia are increasingly implicated in neurological disorders including Alzheimers disease, Parkinsons disease and multiple sclerosis, among many others. However, research into the role of human microglia in these disorders has long been hampered by the inability to obtain them from the human nervous system.

This new protocol now enables scientists around the world to generate this critical cell type from individual patients and improve our understanding of the role of microglia neurological malfunction. NYSCFs mission is to bring cures to patients faster, said Susan L. Solomon, CEO and cofounder of NYSCF. One way we work towards this goal is by developing methods and models that lift the entire field of stem cell research. This new protocol is the perfect example of the type of method that will enable researchers around the world to accelerate their work.

Published in Stem Cell Reports, this microglia protocol is optimized for use in high-throughput experiments, such as drug screening and toxicity testing among other large-scale research applications, and has the benefit of allowing such experiments to be carried out on multiple patient samples. The scientists determined that the protocol is robust and reproducible, generating microglia from sixteen induced pluripotent stem (iPS) cell lines, stem cells that are created from individual patients.

Microglia from humans have long been a desired research model, but are difficult to obtain for laboratory experiments. The NYSCF protocol provides a new source of human microglia cells, which can be generated from disease patient samples and will complement studies in mouse models to better understand the role of microglia in health and disease. Microglia generated by the NYSCF protocol will thus provide a critical tool to investigate microglia dysfunction in central nervous system disorders and advance complex disease modeling in a dish.

This article has been republished frommaterialsprovided byNYSCF. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Microglia Generation For High-Throughput Experiments Optimized - Technology Networks

Cancer Immunotherapy May Work in Unexpected Way – Laboratory Equipment

By Stem Cell Medical Center

Antibodies to the proteins PD-1 and PD-L1 have been shown to fight cancer by unleashing the body's T cells, a type of immune cell. Now, researchers at the Stanford University School of Medicine have shown that the therapy also fights cancer in a completely different way, by prompting immune cells called macrophages to engulf and devour cancer cells.

The finding may have important implications for improving and expanding the use of this cancer treatment, the researchers said.

A study describing the work, which was done in mice, was published online May 17 in Nature. The senior author is Irving Weissman, MD, professor of pathology and of developmental biology. The lead author is graduate student Sydney Gordon.

PD-1 is a cell receptor that plays an important role in protecting the body from an overactive immune system. T cells, which are immune cells that learn to detect and destroy damaged or diseased cells, can at times mistakenly attack healthy cells, producing autoimmune disorders like lupus or multiple sclerosis. PD-1 is what's called an "immune checkpoint," a protein receptor that tamps down highly active T cells so that they are less likely to attack healthy tissue.

How cancer hijacks PD-1

About 10 years ago, researchers discovered that cancer cells learn to use this immune safeguard for their own purposes. Tumor cells crank up the production of PD-L1 proteins, which are detected by the PD-1 receptor, inhibiting T cells from attacking the tumors. In effect, the proteins are a "don't kill me" signal to the immune system, the Stanford researchers said. Cancer patients are now being treated with antibodies that block the PD-1 receptor or latch onto its binding partner, PD-L1, to turn off this "don't kill me" signal and enable the T cells' attack.

"Using antibodies to PD-1 or PD-L1 is one of the major advances in cancer immunotherapy," said Weissman, who is also the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and director of the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford. "While most investigators accept the idea that anti-PD-1 and PD-L1 antibodies work by taking the brakes off of the T-cell attack on cancer cells, we have shown that there is a second mechanism that is also involved."

What Weissman and his colleagues discovered is that PD-1 activation also inhibits the anti-cancer activity of other immune cells called macrophages. "Macrophages that infiltrate tumors are induced to create the PD-1 receptor on their surface, and when PD-1 or PD-L1 is blocked with antibodies, it prompts those macrophage cells to attack the cancer," Gordon said.

Similar to anti-CD47 antibody

This mechanism is similar to that of another antibody studied in the Weissman lab: the antibody that blocks the protein CD47. Weissman and his colleagues showed that using anti-CD47 antibodies prompted macrophages to destroy cancer cells. The approach is now the subject of a small clinical trial in human patients.

As it stands, it's unclear to what degree macrophages are responsible for the therapeutic success of the anti-PD-1 and anti-PD-L1 antibodies.

The practical implications of the discovery could be important, the researchers said. "This could lead to novel therapies that are aimed at promoting either the T-cell component of the attack on cancer or promoting the macrophage component," Gordon said.

Another implication is that antibodies to PD-1 or PD-L1 may be more potent and broadly effective than previously thought. "In order for T cells to attack cancer when you take the brakes off with antibodies, you need to start with a population of T cells that have learned to recognize specific cancer cells in the first place," Weissman said. "Macrophage cells are part of the innate immune system, which means they should be able to recognize every kind of cancer in every patient."

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Cancer Immunotherapy May Work in Unexpected Way - Laboratory Equipment

Basis of ‘leaky’ brain blood vessels in Huntington’s disease identified – UCI News

By Stem Cell Medical Center

Irvine, Calif., May 16, 2017 By using induced pluripotent stem cells to create endothelial cells that line blood vessels in the brain for the first time for a neurodegenerative disease, University of California, Irvine neurobiologists and colleagues have learned why Huntingtons disease patients have defects in the blood-brain barrier that contribute to the symptoms of this fatal disorder.

Now we know there are internal problems with blood vessels in the brain, said study leader Leslie Thompson, UCI professor of psychiatry & human behavior and neurobiology & behavior. This discovery can be used for possible future treatments to seal the leaky blood vessels themselves and to evaluate drug delivery to patients with HD.

The blood-brain barrier protects the brain from harmful molecules and proteins. It has been established that in Huntingtons and other neurodegenerative diseases there are defects in this barrier adding to HD symptoms. What was not known was whether these defects come from the cells that constitute the barrier or are secondary effects from other brain cells.

To answer that, Thompson and colleagues from UCI, Columbia University, the Massachusetts Institute of Technology and Cedars-Sinai Medical Center reprogrammed cells from HD patients into induced pluripotent stem cells, then differentiated them into brain microvascular endothelial cells those that form the internal lining of blood vessels and prevent leakage of blood proteins and immune cells.

The researchers discovered that blood vessels in the brains of HD patients become abnormal due to the presence of the mutated Huntingtin protein, the hallmark molecule linked to the disease. As a result, these blood vessels have a diminished capacity to form new blood vessels and are leaky compared to those derived from control patients.

The chronic production of the mutant Huntingtin protein in the blood vessel cells causes other genes within the cells to be abnormally expressed, which in turn disrupts their normal functions, such as creating new vessels, maintaining an appropriate barrier to outside molecules, and eliminating harmful substances that may enter the brain.

In addition, by conducting in-depth analyses of the altered gene expression patterns in these cells, the study team identified a key signaling pathway known as the Wnt that helps explain why these defects occur. In the healthy brain, this pathway plays an important role in forming and preserving the blood-brain barrier. The researchers showed that most of the defects in HD patients blood vessels can be prevented when the vessels are exposed to a compound (XAV939) that inhibits the activity of the Wnt pathway.

This is the first induced pluripotent stem cell-based model of the blood-brain barrier for a neurodegenerative disease. The study appears in the journal Cell Reports, with a parallel study from Cedars-Sinai Medical Center in Cell Stem Cell that advances the first model for a neurodevelopmental disease that specifically affects the blood-brain barrier.

These studies together demonstrate the incredible power of iPSCs to help us more fully understand human disease and identify the underlying causes of cellular processes that are altered, said Ryan Lim, a postgraduate research scientist at the Institute for Memory Impairments and Neurological Disorders, or UCI MIND, who initiated the UCI work.

We show a proof-of-concept therapy where we could reverse some of the abnormalities in the blood vessel cells by treating them with a drug, added Thompson, who is affiliated with both UCI MIND and the Sue & Bill Gross Stem Cell Research Center.

The future direction of this study is to develop ways to test how drugs may be delivered to the brain of HD patients and to examine additional treatment strategies using our understanding of the underlying causes of abnormalities in brain blood vessels, said study co-leader Dritan Agalliu, assistant professor of pathology & cell biology at Columbia University Medical Center.

Chris Quan, Andrea M. Reyes-Ortiz, Jie Wu, Jennifer Stocksdale and Malcolm S. Casale of UCI; Amanda J. Kedaigle, Theresa A. Gipson, Ernest Fraenkel and David E. Housman of MIT; Gad D. Vatine and Clive N. Svendsen of Cedars-Sinai; and Sarah E. Lutz of Columbia University also contributed to the study, which was supported in part by the American Heart Association, California Institute for Regenerative Medicine and National Institutes of Health.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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Basis of 'leaky' brain blood vessels in Huntington's disease identified - UCI News

Lab-Grown Blood Stem Cells Produced at Last – Scientific American

By Stem Cell Clinic

After 20 years of trying, scientists have transformed mature cells into primordial blood cells that regenerate themselves and the components of blood. The work, described today inNature, offers hope to people with leukaemia and other blood disorders who need bone-marrow transplants but cant find a compatible donor. If the findings translate into the clinic, these patients could receive lab-grown versions of their own healthy cells.

One team, led by stem-cell biologist George Daley of Boston Childrens Hospital in Massachusetts, created human cells that act like blood stem cells, although they are not identical to those found in nature. A second team, led by stem-cell biologist Shahin Rafii of Weill Cornell Medical College in New York City, turned mature cells from mice into fully fledged blood stem cells.

For many years, people have figured outparts of this recipe, but theyve never quite gotten there, says Mick Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, who was not involved with either study. This is the first time researchers have checked all the boxes and made blood stem cells.

Daleys team chose skin cells and other cells taken from adults as their starting material. Using a standard method, they reprogrammed the cells intoinduced pluripotent stem (iPS) cells, which are capable of producing manyother cell types. Until now, however, iPS cells have not been morphed into cells that create blood.

The next step was the novel one: Daley and his colleagues inserted seven transcription factorsgenes that control other genesinto the genomes of the iPS cells. Then they injected these modified human cells into mice to develop. Twelve weeks later, the iPS cells had transformed into progenitor cells capable of making the range of cells found in human blood, including immune cells. The progenitor cells are tantalizingly close to naturally occurring haemopoetic blood stem cells, says Daley.

Bhatia agrees. Its pretty convincing that George has figured out how to cook up human haemopoetic stem cells, he says. That is the holy grail.

By contrast, Rafiis team generated true blood stem cells from mice without the intermediate step of creating iPS cells. The researchers began by extracting cells from the lining of blood vessels in mature mice. They then inserted four transcription factors into the genomes of these cells, and kept them in Petri dishes designed to mimic the environment inside human blood vessels. There, the cells morphed into blood stem cells and multiplied.

When the researchers injected these stem cells into mice that had been treated with radiation to kill most of their blood and immune cells, the animals recovered. The stem cells regenerated the blood, including immune cells, and the mice went on to live a full lifemore than 1.5 years in the lab.

Because he bypassed the iPS-cell stage, Rafii compares his approach to a direct aeroplane flight, and Daleys procedure to a flight that takes a detour to the Moon before reaching its final destination. Using the most efficient method to generate stem cells matters, he adds, because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumours if they are implanted into people.

But Daley and other researchers are confident that the method he used can be made more efficient, and less likely to spur tumour growth and other abnormalities in modified cells. One possibility is to temporarily alter gene expression in iPS cells, rather than permanently insert genes that encode transcription factors, says Jeanne Loring, a stem-cell researcher at the Scripps Research Institute in La Jolla, California. She notes that iPS cells can be generated from skin and other tissue that is easy to access, whereas Rafiis method begins with cells that line blood vessels, which are more difficult to gather and to keep alive in the lab.

Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS cells. A lot of people have become jaded, saying that these cells dont exist in nature and you cant just push them into becoming anything else, Bhatia says. I hoped the critics were wrong, and now I know they were.

This article is reproduced with permission and wasfirst publishedon May 17, 2017.

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Lab-Grown Blood Stem Cells Produced at Last - Scientific American

Asymmetrex Named One of the "50 Most Valuable Brands of the Year 2017" by The Silicon Review – Benzinga

By Stem Cell Clinic

Yesterday, when Silicon Valley magazine The Silicon Review announced its 2017 class of 50 Most Valuable Brands, one member, private stem cell biotechnology start-up Asymmetrex, may have seemed an unusual selection. However, the company's unique in silico approach to counting therapeutic tissue stem cells earned it this recognition.

Boston, MA (PRWEB) May 18, 2017

When James Sherley, was notified earlier this year that his company Asymmetrex had been selected as one of the 50 Most Valuable Brands for the Year 2017 by The Silicon Review, he was not surprised as others might be. Sherley says, "I felt like we had been making good progress increasing Asymmetrex's value, but this recognition by Silicon Valley was particularly meaningful. Our selection by The Silicon Review may seem odd to some, but it makes perfect sense to us. We are able to count adult tissue stem cells for the first time, how? By adapting and designing in silico computational simulation techniques to reveal previously unmeasured properties of adult tissue stem cells, like for instance their number!"

Sherley had a theoretical concept for counting tissue stem cells since before he and his collaborators published a 2001 seminal report explaining how the culture of human tissue cells depends on the unique cell production abilities of tissue stem cells. However, implementing and testing his concept would require enlisting computational modeling expertise. Although Sherley was a professor at MIT, during his time there from 1998 to 2007, he was able to entice only one computer science graduate student to work with him on the idea as a half-semester interdisciplinary experience project.

Then Sherley met Frank Abdi, Ph.D. at a biology-mesomechanics integrative conference in Vicenza, Italy in 2011. Abdi is the founder and chief scientist at AlphaSTAR Corporation, a leading global consulting company in the aircraft and aerospace industry. In AlphaSTAR, Abdi had developed an award-winning, proprietary suite of statistical computational software for simulating the complex behavior of composite materials in high mechanical stress crafts like airplanes, racing cars, and space shuttles. Abdi had a long-standing interest in applying these malleable computational tools to problems in medicine. So, it did not take long for Abdi and Sherley to recognize that they were the ideal team to advance Sherley's computational tissue stem cell counting concept to practical use.

With other AlphaSTAR staff, the two began by translating Sherley's biological models into computational code. When Asymmetrex was formed in 2013, the two companies added staff and resources to accelerate their efforts to develop and validate the new counting approach. By the middle of 2016, they had completed development of the AlphaSTEM Test, a working software program validated for counting tissue stem cells in human lung, bone marrow, liver, and amniotic fluid, as well as for detecting tissue stem cell-active compounds like drug candidates. The data input required for the AlphaSTEM Test is easily obtained total cell count data from serial culture of dissociated human tissue cells.

Asymmetrex now markets the AlphaSTEM Test with the computing support of AlphaSTAR. Before the AlphaSTEM Test, there was no method available for counting adult tissue stem cells specifically. Now, it is possible to count tissue stem cells in experiments in research labs; to determine the dose of stem cells in approved stem cell therapies; to determine the quality and dose of stem cells used in private stem cell clinic treatments; to determine stem cell dose for better interpretation of stem cell clinical trial results; to monitor and optimize biomanufacturing processes for therapeutic tissue stem cells; to determine the dose of genetically-engineered stem cells in gene and gene editing therapies; to have earlier screening for stem cell-toxic drugs that fail in clinical trials because of chronic organ failure; to identify environmental toxicants that alter tissue stem cells; and to identify compounds that improve health by positive effects on tissue stem cells.

The many benefits that will flow from now being able to address these many waiting unmet needs and markets are the basis for The Silicon Review's recognition of Asymmetrex's high value in 2017 and beyond.

About Asymmetrex

Asymmetrex, LLC is a Massachusetts life sciences company with a focus on developing technologies to advance stem cell medicine. Asymmetrex's founder and director, James L. Sherley, M.D., Ph.D. is an internationally recognized expert on the unique properties of adult tissue stem cells. The company's patent portfolio contains biotechnologies that solve the two main technical problems production and quantification that have stood in the way of successful commercialization of human adult tissue stem cells for regenerative medicine and drug development. In addition, the portfolio includes novel technologies for isolating cancer stem cells and producing induced pluripotent stem cells for disease research purposes. Currently, Asymmetrex's focus is employing its technological advantages to develop and market facile methods for monitoring adult stem cell number and function in stem cell transplantation treatments and in pre-clinical assays for drug safety.

For the original version on PRWeb visit: http://www.prweb.com/releases/2017/05/prweb14347779.htm

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Asymmetrex Named One of the "50 Most Valuable Brands of the Year 2017" by The Silicon Review - Benzinga

Major ‘Milestone’ Realized in Quest to Transform Stem Cells Into Blood Cells – Seeker

By Embryonic Stem Cells

Scientists on Wednesday unveiled two methods for coaxing stem cells into blood cells, a long-sought goal that could lead to new treatments for blood disease, including leukemia.

In separate experiments reported in Nature one with mice, the other transplanting human stem cells into mouse bone marrow researchers demonstrated techniques with the potential to produce all types of blood cells.

This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect, and make functional blood cells, said Ryohichi Sugimura, a doctor at Boston Children's Hospital and lead author of one of the studies.

If proven safe, the proof-of-concept methods could also lead to a limitless supply of blood by using cells from universal donors, he added.

Human embryonic stem cells generic cells which, as the embryo develops, gradually differentiate were first isolated in 1998.

A decade later, scientists figured out how to generate another type of all-purpose cell from human skin, known as induced pluripotent stem cells, or iPS. These were successfully used to make neurons and heart cells.

But the goal of creating blood-forming stem cells in the lab remained out-of-reach.

RELATED: Blood From Human Babies, Teens Rejuvenates Old Mice

Sugimura and colleagues devised a three-step process to achieve that breakthrough.

They began by inducing both embryonic stems cells and iPS to morph into a form of embryonic tissue that in a natural process gives rise to blood stem cells. This had been done before.

In the second crucial step, they experimented with dozens of proteins known to control gene expression, especially during the formative process of embryo growth.

Protein cocktail They found that five of these so-called transcription factors, working together, yielded the elusive blood stem cells the starter kit for white and red blood cells, platelets, macrophages and all the other cell types of which blood is composed.

Finally, they transplanted these human blood stem cells into the bone marrow of live mice.

Within a few weeks, several kinds of human blood cells had formed, and were circulating in the rodents.

We are now able to model human blood function in so-called humanized mice, said George Daley, head of a research lab at Boston Children's Hospital and the main architect of the experiment, in a statement.

We're tantalizingly close to generating bona fide human blood cells in a dish, he added.

In the second study, a team led by Shahin Rafii at Weill Cornell Medicine in New York City used adult mouse cells as their starting material, and then guided them through several steps including exposure to some of the same gene-activating proteins to create mature blood stem cells in a petri dish.

RELATED:Vampire Bats Are Drinking Human Blood in Brazil

Taken together, the two experiments represent a milestone in stem cell development, said Carolina Guibentif and Berthold Gottgens, researchers at the Cambridge Stem Cell Institute in England who did not participate in the work.

The ability to manufacture HSCs haematopoietic, or blood, stem cells in the laboratory holds enormous promise for cell therapy, drug screening and studies of leukaemia development, they wrote in a commentary, also published by Nature.

A key concern, they noted, was the possible risk associated with using transcription factors that may themselves be linked to the early stages of leukemia.

How these cocktails of catalyzing proteins are inserted into developing tissue is of particular concern.

But new techniques of ultra-precise gene-editing, they added, could soon render such potential problems obsolete.

WATCH: How Do Blood Transfusions Work?

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Major 'Milestone' Realized in Quest to Transform Stem Cells Into Blood Cells - Seeker

Let there be tissue: More precise, controlled method of engineering tissues from stem cells – Science Daily

By Embryonic Stem Cells

Science Daily
Let there be tissue: More precise, controlled method of engineering tissues from stem cells
Science Daily
A major promise of studying human embryonic stem cells is to understand these processes and apply the knowledge toward tissue engineering. Researchers in UC Santa Barbara's departments of Chemistry and Biochemistry, and of Molecular, Cellular and ...

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Let there be tissue: More precise, controlled method of engineering tissues from stem cells - Science Daily

No research justifies the use of human embryos, Pope Francis says – Catholic News Agency

By Embryonic Stem Cells

Vatican City, May 18, 2017 / 10:26 am (CNA/EWTN News).- Pope Francis said that there is no outcome that can justify the use or destruction of embryos for scientific purposes even for the commendable cause of trying to help those suffering from incurable diseases.

Some branches of research, in fact, utilize human embryos, inevitably causing their destruction. But we know that no ends, even noble in themselves, such as a predicted utility for science, for other human beings or for society, can justify the destruction of human embryos, he said May 18.

Pope Francis spoke during a meeting at the Vatican Thursday with people affected by a rare and incurable genetic brain disorder called Huntingtons disease, along with their families and caretakers.

His comments were significant given the massive slate of members from the medical and scientific communities who treat the patients with Huntington's and perform research on how to prevent the disease or slow its progression. Present were some 1,700 people from 16 different countries. Sponsors for the event included major corporations such as Virgin Airlines.

There are several ethical problems surrounding the research on Huntingtons disease, including the use of embryonic stem cells taken from embryos made through in vitro fertilization.

The Pope noted this fact during the audience, encouraging scientists to pursue scientific advancement only through means that do not contribute to the throw-away culture which treats human beings as objects for use.

The is not the first time Francis has spoken out against embryonic stem cell research. In his 2015 environment encyclical Laudato Si, he decried a tendency within the field of science to justify transgressing all boundaries when experimentation is carried out on living human embryos.

We forget that the inalienable worth of a human being transcends his or her degree of development, he said, adding that once technology disregards ethical principles, it ends up considering any practice whatsoever as licit.

When we fail to acknowledge as part of reality the worth of a poor person, a human embryo, a person with disabilities to offer just a few examples it becomes difficult to hear the cry of nature itself; everything is connected.

Once the human being seeks absolute dominion, the foundations of our life begin to crumble, the Pope said in Laudato Si, so that instead of cooperating with God, man puts himself in Gods place and thus ends up provoking a rebellion on the part of nature.

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No research justifies the use of human embryos, Pope Francis says - Catholic News Agency

Comprehensive cancer study assesses potential targets for personalized medicine and finds new ones – Medical Xpress

By Uncategorized

May 18, 2017 Dr. Chad Creighton. Credit: Baylor College of Medicine

Looking to improve cancer treatment, a multi-institutional research team has taken a comprehensive approach to evaluating which molecular changes in cancer cells are most likely involved in the development of the disease. This approach resulted in the confirmation of previously known cancer molecular changes and in the discovery of others that had not been typically linked to cancer before. Targeting particular patient alterations with specific drugs might help one day improve response to treatment. The report appears in Cancer Cell.

"We studied the PI3K pathway, one of the most important pathways of the cell," said senior author Dr. Chad Creighton, associate professor of medicine and member of the Dan L Duncan Comprehensive Cancer Center Division of Biostatistics at Baylor College of Medicine. "A cellular pathway is a chain of events involving several proteins. The PI3K pathway has a number of diverse functions, including altering the cell's metabolism and driving cell growth and proliferation."

"PI3K is the most commonly mutated pathway in cancer that can be targeted by drugs. Thus, understanding how the pathway and mutations in cancer affect the many different cancer lineages is important," said co-author Dr. Gordon Mills, professor of medicine and immunology at MD Anderson Cancer Center.

Previous studies had identified a number of the genes, proteins and processes involved in the PI3K pathway in cells grown in the lab.

"In this study, we have taken what we have learned in the lab regarding how the pathway works and analyzed it together with information about the genes and the proteins present in cancer cells taken from human patients," Creighton said. "We looked at nearly 11,000 human cancers representing 32 major types. This is the largest study of its kind, and it was possible in part thanks to the Cancer Genome Atlas, a publicly available dataset of genomic changes in 32 types of cancer."

To carry out the complex analysis of this vast amount of data, the research team pulled the resources of experts in cancer protein data, in molecular biology of the pathway, and in the use of powerful analytical tools that provided genomic analysis and integration of the protein data.

The challenge is to know which mutations in cancer are important

To assess which cancer mutations are important, the researchers carried out a comprehensive analysis that allowed them to distinguish which of the altered genes and proteins were more likely to affect the normal function of the PI3K pathway.

"What makes this analysis complex is that there is a large number of gene and protein alterations that can be present in a given patient's tumor, and it is possible that different alterations are present in different patients," Creighton said. "In addition, not all mutations necessarily cause disease. The challenge is to find out which mutations are altering the pathway in a way that can lead to cancer. We hope that one day we will be able to apply this knowledge to personalized medicine."

There were a few surprises in the study.

"For some genes there was previous work indicating they were implicated in this pathway, but we discovered other genes, such as IDH1 and VHL, which had not been typically associated with the pathway in cancer before," Creighton said. "These genes, as well as others that may be discovered in the future, may now be incorporated into the group of genes linked to the PI3K pathway and considered as potential candidates for targeted therapy."

"Finding several cancers and mutations that we didn't know before could activate this pathway supports moving up the priority of testing drugs toward the new mutations found in specific cancer types," said co-author Dr. David Kwiatkowski, professor of medicine at Harvard Medical School and senior physician at Brigham and Women's Hospital and the Dana Farber Cancer Institute.

The future of personalized medicine

"The comprehensive nature of this project that integrates information from multiple levels has the potential to impact patient management and to eventually improve outcomes for the large population of patients with abnormalities in this very important pathway," Mills said.

"This comprehensive approach expands our knowledge regarding which types of cancer this pathway is activated and why, and that's important in terms of thinking about therapies that go after this pathway," Kwiatkowski said.

Imagine the following possible future scenario in a personalized medicine setting: a patient provides a sample of tumor and the physician sends it to a lab that runs a sequencing assay that shows where the genetic changes are located and the type of changes. Then, from the protein data, the team of physicians and scientists can determine which genetic changes are associated with greater activation of the PI3K pathway and which may not. These data would help the team in terms of selecting patients for whom specific drugs may be effective.

Explore further: New subtypes of lung cancer can lead to personalized therapies with better outcome

More information: Cancer Cell (2017). DOI: 10.1016/j.ccell.2017.04.013

Personalized therapies can potentially improve the outcomes of patients with lung cancer, but how to best design such an approach is not always clear. A team of scientists from Baylor College of Medicine and the University ...

Understanding the complexity of cancer is a major goal of the scientific community, and for kidney cancer researchers this goal just got closer. Dr. Chad Creighton, associate professor of medicine and member of the Dan L ...

Breast cancer's ability to develop resistance to treatment has frustrated researchers and physicians and has thwarted even the latest and greatest targeted therapies. For example, after researchers identified a disease pathway ...

Researchers at the Institute of Biomedical Investigation of Bellvitge (IDIBELL), led by Dr. Mariona Graupera, have unveiled the potential therapeutic benefit of a selective inhibitior of the PI3-kinase (PI3K) protein in pancreatic ...

A protein known to play a role in transporting the molecular contents of normal cells into and out of various intracellular compartments can also turn such cells cancerous by stimulating a key growth-control pathway.

Cancer cells often devise ways to survive even in the presence of toxic chemotherapy. Now, a research team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has found a way to attack a process that tumor ...

Looking to improve cancer treatment, a multi-institutional research team has taken a comprehensive approach to evaluating which molecular changes in cancer cells are most likely involved in the development of the disease. ...

Antibodies to the proteins PD-1 and PD-L1 have been shown to fight cancer by unleashing the body's T cells, a type of immune cell. Now, researchers at the Stanford University School of Medicine have shown that the therapy ...

Eating certain kinds of tree nuts, such as almonds, pecans, walnuts, hazelnuts and cashews, has been linked to a dramatically lower risk of colon cancer recurrence, researchers said Wednesday.

Researchers at The University of Manchester have discovered that a protein (5T4) found on the surface of cells contributes to chemotherapy resistance in the most common type of childhood leukaemia. Using a novel approach, ...

The HPV vaccine that helps prevent cervical cancer in women also might lower the risk in young men of oral infections that can cause mouth and throat cancers, a new study finds.

University of Georgia researchers, with colleagues from the University of Tokyo, have identified a new drug target for the two most common types of myeloid leukemia, including a way to turn back the most aggressive form of ...

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Comprehensive cancer study assesses potential targets for personalized medicine and finds new ones - Medical Xpress

NantKwest Appoints Dr. John Lee as Senior Vice President of Adult Medical Affairs – Business Wire (press release)

By Uncategorized

CULVER CITY, Calif.--(BUSINESS WIRE)--NantKwest Inc.(NASDAQ:NK), a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases, announced todaythe appointment ofJohn Lee, MD, FACS, as Senior Vice President of Adult Medical Affairs.In his new role, Dr. Lee will oversee regulatory strategy for clinical trials, medical writing and translation of pre-clinical science into the development of new trials.

Adding Dr. Lee to our adult medical affairs team will help accelerate our efforts towards bringing impactful clinical trials to life,said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest. As an esteemed medical professor and surgeon with extensive experience in oncology research, Dr. Lees leadership will be crucial to advancing the development of effective immunotherapy treatments.

In addition to joining NantKwest, Dr. Lee currently serves as Co-Director of the Chan Soon-Shiong Institute of Medicine, and has been asurgical oncologist with Sanford Health since 2008.

Our ultimate goal is to reduce the overall cancer mortality rate by leveraging the bodys immune system to combat all types of cancer, said Dr. Lee. From our recent authorization from the U.S. Food & Drug Administration (FDA) for an Investigational New Drug (IND) application for the NANT Cancer Vaccine, to our partnership with Viracta Therapeutics, Inc. to combine our platform of natural killer (NK) cell therapies with the companys Phase 2 drug candidate, Im thrilled to be a part of a company that is on its way to revolutionizing the way we treat this complex disease.

Dr. Lees prior experience at Sanford Health was largely focused on developing a comprehensive head and neck cancer program aimed at bringing immuno-oncology drugs to patients. In addition, as medical director of cancer research, he helped develop several other cancer multi-disciplinary teams that focused on clinical and research excellence. By initiating and overseeing the health systems protocol review committee for all incoming oncology trials, Dr. Lee has developed several clinical trials within Sanford. Throughout his time there, he was promoted to full professor and Dr. Lees lab produced more than 40 peer-reviewed papers, multiple patents and helped increase institutional funded research from the National Institutes of Health (NIH). His surgical training in head and neck surgery was completed at the University of Iowa, where he was eventually promoted to associate professor. Dr. Lee received his MD from the University of Minnesota and completed his undergraduate education at Stanford University.

About NantKwest

NantKwest (NASDAQ:NK) is a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases. NK cells are the bodys first line of defense due to the innate ability of NK cells to rapidly identify and destroy cells under stress, such as cancer or virally-infected cells.

NantKwests unique NK cell-based platform, with the capacity to grow active killer cells as a biological cancer therapy, has been designed to induce cell death against cancer or infected cells by three different modes of action: (1) Direct killing using activated NK cells (aNK) that release toxic granules directly into the cell through cell to cell contact; (2) Antibody-mediated killing using haNKs, which are NK cells engineered to incorporate a high affinity receptor that binds to an administered antibody, enhancing the cancer cell killing effect of that antibody; and (3) Chimeric Antigen Receptor (CAR) activated killing using taNKs, which are NK cells engineered to incorporate CARs to target tumor-specific antigens found on the surface of cancer cells.

Our aNK, haNK and taNK platform addresses certain limitations of T cell therapies, including the reduction of risk of serious cytokine storms reported after T cell therapy. As an off-the-shelf therapy, NantKwests NK cells do not rely on a patients own often compromised immune system. In Phase 1 clinical trials in patients with late stage cancer, NantKwests NK cells have been successfully administered as an outpatient infusion therapy without any reported severe side effects, even at doses of 10 billion cells.

By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs that include a Phase 2 trial for a rare form of melanoma and the planned initiation of a clinical trial of NK cells targeted to breast cancer, we believe NantKwest is uniquely positioned to be the premier immunotherapy company and transform medicine by delivering living drugs in a bag and bringing novel NK cell-based therapies to routine clinical care. For more information please visit http://www.nantkwest.com and follow Dr. Soon-Shiong on Twitter @DrPatSoonShiong.

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NantKwest Appoints Dr. John Lee as Senior Vice President of Adult Medical Affairs - Business Wire (press release)

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