Scientists create stem cell therapy for lung fibrosis conditions

A team of scientists from the UNC School of Medicine and North Carolina State University (NCSU) has developed promising research towards a possible stem cell treatment for several lung conditions, such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis — often-fatal conditions that affect tens of millions of Americans.

In the journal Respiratory Research, the scientists demonstrated that they could harvest lung stem cells from people using a relatively non-invasive, doctor’s-office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy.

In a second study, published in the journal Stem Cells Translational Medicine, the team showed that in rodents they could use the same type of lung cell to successfully treat a model of IPF – a chronic, irreversible, and ultimately fatal disease characterized by a progressive decline in lung function.

The researchers have been in discussions with the FDA and are preparing an application for an initial clinical trial in patients with IPF.

“This is the first time anyone has generated potentially therapeutic lung stem cells from minimally invasive biopsy specimens,” said co-senior author of both papers Jason Lobo, MD, an assistant professor of medicine at UNC and medical director of lung transplant and interstitial lung disease.

Co-senior author Ke Cheng, PhD, an associate professor in NCSU’s Department of Molecular Biomedical Sciences and the UNC/NCSU Joint Department of Biomedical Engineering, said, “We think the properties of these cells make them potentially therapeutic for a wide range of lung fibrosis diseases.”

These diseases of the lung involve the buildup of fibrous, scar-like tissue, typically due to chronic lung inflammation. As this fibrous tissue replaces working lung tissue, the lungs become less able to transfer oxygen to the blood. Patients ultimately are at risk of early death from respiratory failure. In the case of IPF, which has been linked to smoking, most patients live for fewer than five years after diagnosis.

The two FDA-approved drug treatments for IPF reduce symptoms but do not stop the underlying disease process. The only effective treatment is a lung transplant, which carries a high mortality risk and involves the long-term use of immunosuppressive drugs.

Scientists have been studying the alternative possibility of using stem cells to treat IPF and other lung fibrosis diseases. Stem cells are immature cells that can proliferate and turn into adult cells in order to, for example, repair injuries. Some types of stem cells have anti-inflammatory and anti-fibrosis properties that make them particularly attractive as potential treatments for fibrosis diseases.

Cheng and Lobo have focused on a set of stem cells and support cells that reside in the lungs and can be reliably cultured from biopsied lung tissue. The cells are called lung spheroid cells for the distinctive sphere-like structures they form in culture. As the scientists reported in an initial paper in 2015, lung spheroid cells showed powerful regenerative properties when applied to a mouse model of lung fibrosis. In their therapeutic activity, these cells also outperformed other non-lung-derived stem cells known as mesenchymal stem cells, which are also under investigation to treat fibrosis.

In the first of the two new studies, Lobo and his team showed that they could obtain lung spheroid cells from human lung disease patients with a relatively non-invasive procedure called a transbronchial biopsy.

“We snip tiny, seed-sized samples of airway tissue using a bronchoscope,” Lobo said. “This method involves far less risk to the patient than does a standard, chest-penetrating surgical biopsy of lung tissue.”

Cheng and his colleagues cultured lung spheroid cells from these tiny tissue samples until they were numerous enough – in the tens of millions – to be delivered therapeutically. When they infused the cells intravenously into mice, they found that most of the cells gathered in the animals’ lungs.

“These cells are from the lung, and so in a sense they’re happiest, so to speak, living and working in the lung,” Cheng said.

In the second study, the researchers first induced a lung fibrosis condition in rats. The condition closely resembled human IPF. Then the researchers injected the new cultured spheroid cells into one group of rats. Upon studying this group of animals and another group treated with a placebo, the researchers saw healthier overall lung cells and significantly less lung inflammation and fibrosis in the rats treated with lung spheroid cells.

“Also, the treatment was safe and effective whether the lung spheroid cells were derived from the recipients’ own lungs or from the lungs of an unrelated strain of rats,” Lobo said. “In other words, even if the donated stem cells were ‘foreign,’ they did not provoke a harmful immune reaction in the recipient animals, as transplanted tissue normally does.”

Lobo and Chen expect that when used therapeutically in humans, lung spheroid cells initially would be derived from the patient to minimize any immune-rejection risk. Ultimately, however, to obtain enough cells for widespread clinical use, doctors might harvest them from healthy volunteers, as well as from whole lungs obtained from organ donation networks. The stem cells could later be used in patients as-is or matched immunologically to recipients in much the same way transplanted organs are typically matched.

“Our vision is that we will eventually set up a universal cell donor bank,” Cheng said.

Cheng, Lobo, and their teams are now planning an initial study of therapeutic lung spheroid cells in a small group of IPF patients and expect to apply later this year for FDA approval of the study. In the long run, the scientists hope their lung stem cell therapy will also help patients with other lung fibrosis conditions of which there are dozens, including COPD, cystic fibrosis, and fibro-cavernous pulmonary tuberculosis.

Cardiac stem cells from heart disease patients may be harmful

Patients with severe and end-stage heart failure have few treatment options available to them apart from transplants and “miraculous” stem cell therapy. But a new Tel Aviv University study finds that stem cell therapy may, in fact, harm heart disease patients.

The research, led by Prof. Jonathan Leor of TAU’s Sackler Faculty of Medicine and Sheba Medical Center and conducted by TAU’s Dr. Nili Naftali-Shani, explores the current practice of using cells from the host patient to repair tissue — and contends that this can prove deleterious or toxic for patients. The study was recently published in the journal Circulation.

“We found that, contrary to popular belief, tissue stem cells derived from sick hearts do not contribute to heart healing after injury,” said Prof. Leor. “Furthermore, we found that these cells are affected by the inflammatory environment and develop inflammatory properties. The affected stem cells may even exacerbate damage to the already diseased heart muscle.”

Tissue or adult stem cells — “blank” cells that can act as a repair kit for the body by replacing damaged tissue — encourage the regeneration of blood vessel cells and new heart muscle tissue. Faced with a worse survival rate than many cancers, many heart failure patients have turned to stem cell therapy as a last resort.

“But our findings suggest that stem cells, like any drug, can have adverse effects,” said Prof. Leor. “We concluded that stem cells used in cardiac therapy should be drawn from healthy donors or be better genetically engineered for the patient.”

Hope for improved cardiac stem cell therapy

In addition, the researchers also discovered the molecular pathway involved in the negative interaction between stem cells and the immune system as they isolated stem cells in mouse models of heart disease. After exploring the molecular pathway in mice, the researchers focused on cardiac stem cells in patients with heart disease.

The results could help improve the use of autologous stem cells — those drawn from the patients themselves — in cardiac therapy, Prof. Leor said.

“We showed that the deletion of the gene responsible for this pathway can restore the original therapeutic function of the cells,” said Prof. Leor. “Our findings determine the potential negative effects of inflammation on stem cell function as they’re currently used. The use of autologous stem cells from patients with heart disease should be modified. Only stem cells from healthy donors or genetically engineered cells should be used in treating cardiac conditions.”

The researchers are currently testing a gene editing technique (CRISPER) to inhibit the gene responsible for the negative inflammatory properties of the cardiac stem cells of heart disease patients. “We hope our engineered stem cells will be resistant to the negative effects of the immune system,” said Prof. Leor.

Stem Cell Treatment May Restore Vision to Patients with Damaged Corneas

Researchers working as part of the University of Georgia’s Regenerative Bioscience Center have developed a new way to identify and sort stem cells that may one day allow clinicians to restore vision to people with damaged corneas using the patient’s own eye tissue. They published their findings in Biophysical Journal.

The cornea is a transparent layer of tissue covering the front of the eye, and its health is maintained by a group of cells called limbal stem cells. But when these cells are damaged by trauma or disease, the cornea loses its ability to self-repair.

“Damage to the limbus, which is where the clear part of the eye meets the white part of the eye, can cause the cornea to break down very rapidly,” said James Lauderdale, an associate professor of cellular biology in UGA’s Franklin College of Arts and Sciences and paper co-author. “The only way to repair the cornea right now is do a limbal cell transplant from donated tissue.”

In their study, researchers used a new type of highly sensitive atomic force microscopy, or AFM, to analyze eye cell cultures. Created by Todd Sulchek, an associate professor of mechanical engineering at Georgia Tech, the technique allowed researchers to probe and exert force on individual cells to learn more about the cell’s overall health and its ability to turn into different types of mature cells.

They found that limbal stem cells were softer and more pliable than other cells, meaning they could use this simple measure as a rapid and cost-effective way to identify cells from a patient’s own tissue that are suitable for transplantation.

“Todd’s technology is unique in the tiniest and most sensitive detection to change,” said Lauderdale. “Just think about trying to gently dimple or prod the top of an individual cell without killing it; with conventional AFM it’s close to impossible.”

Building on their findings related to cell softness, the research team also developed a microfluidic cell sorting device capable of filtering out specific cells from a tissue sample.

With this device, the team can collect the patient’s own tissue, sort and culture the cells and then place them back into the patient all in one day, said Lauderdale. It can take weeks to perform this task using conventional methods.

The researchers are quick to caution that more tests must be done before this technique is used in human patients, but it may one day serve as a viable treatment for the more than 1 million Americans that lose their vision to damaged corneas every year.

The group first started this research with the hope of helping children with aniridia, an inherited malformation of the eye that leads to breakdown of the cornea at an early age.

Because aniridia affects only one in 60,000 children, few organizations are willing to commit the resources necessary to combat the disease, Lauderdale said.

“Our first goal in working with such a rare disease was to help this small population of children, because we feel a close connection to all of them,” says Lauderdale, who has worked with aniridia patients for many years. “However, at the end of the day this technology could help hundreds of thousands of people, like the military who are also interested in corneal damage, common in desert conditions.”

Steven Stice, a Georgia Research Alliance Eminent Scholar, who plays an important role in fostering cross-interdisciplinary collaboration as director of the RBC, initially brought the researchers together and encouraged a seed grant application through the center for Regenerative Engineering and Medicine, or REM, a joint collaboration between Emory University, Georgia Tech and UGA.

“A culture is developing around seed funding that is all about interdisciplinary collaboration, sharing of resources, and coming together to make things happen,” said Stice. “Government funding agencies place a high premium on combining skills and disciplines. We can no longer afford to work in an isolated laboratory using a singular approach.”

The REM seed funding program is intended to stimulate new, unconventional collaborative research and requires equal partnership of faculty from two of the participating institutions.

“We tend to get siloed experimentally,” says Lauderdale. “To a biologist like me, all cells are very different and all atomic force microscopes are the same. To an engineer like Todd it’s just the opposite.”

Tissue Engineering Advance Reduces Heart Failure in Model of Heart Attack

Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer. The cells organized themselves in the scaffold to create engineered heart tissue that beats synchronously in culture. When the human-derived heart muscle patch was surgically placed onto a mouse heart after a heart attack, it significantly improved heart function and decreased the amount of dead heart tissue.

“Our novel technique is the first to achieve resolution of 1 micrometer or less,” the researchers reported in the journal Circulation Research. This tissue engineering advance is an important step toward the goal of preventing heart failure after a heart attack. Such heart failures account for nearly half of the 7.3 million worldwide heart disease-related deaths each year.

The heart cannot regenerate muscle tissue after a heart attack has killed part of the muscle wall. That dead tissue can strain surrounding muscle, leading to a lethal heart enlargement. It has long been the dream of heart experts to create new tissue that could replace damaged muscle and protect the heart from dilatation after a heart attack.

The researchers, led by Jianyi “Jay” Zhang, M.D., Ph.D., the University of Alabama at Birmingham, and Brenda Ogle, Ph.D., the University of Minnesota, modeled the scaffold after a three-dimensional scan of the extracellular matrix of a piece of mouse myocardial tissue. Extracellular matrix is the collection of compounds secreted by cells that gives structural support and cushioning to hold the tissue together.

Using multiphoton three-dimensional printing, the team then created crosslinks among extracellular proteins dissolved in a photoreactive gelatin. When the uncrosslinked gelatin was washed away, the photopolymerized extracellular protein scaffold that remained replicated the shape of the extracellular matrix, with hollows where cells had been.

This native-like scaffold was seeded with a mix of 50,000 cardiomyocytes, smooth muscle cells and endothelial cells derived from human-induced pluripotent stem cells, or hiPSCs. This cardiac muscle patch, about four one-thousandths of an inch thick and eight one-hundredths of an inch square began beating within one day of seeding, and the speed and strength of contractions increased significantly over the next week.

Researchers found that the scaffold had aligned the muscle cells properly, similar to native heart tissue, and the cells showed a smooth wave of electrical signal moving across the patch, a vital part of the electrophysiology that propagates contraction of the heart across the atria or ventricles. It appeared that the native-like structure of the scaffold contributed to the healthy electrical and mechanical function of the cells.

When two of the patches were transplanted onto an infarcted mouse heart, there was significant improvement in measures of cardiac function, blood vessel density and cell proliferation, and reduced infarct size and programmed cell death, or apoptosis.

“Thus, the hiPSC-derived cardiac muscle patches produced for this report may represent an important step toward the clinical use of 3-D-printing technology,” Zhang, Ogle and colleagues wrote. They also said, “To our knowledge, this is the first time modulated raster scanning has ever been successfully used to control the fabrication of a tissue-engineered scaffold, and consequently, our results are particularly relevant for applications that require the fibrillar and mesh-like structures present in cardiac tissue.”

Synthetic Stem Cells Could Offer Therapeutic Benefits, Reduced Risks

Researchers from North Carolina State University, the University of North Carolina at Chapel Hill and First Affiliated Hospital of Zhengzhou University have developed a synthetic version of a cardiac stem cell. These synthetic stem cells offer therapeutic benefits comparable to those from natural stem cells and could reduce some of the risks associated with stem cell therapies. Additionally, these cells have better preservation stability and the technology is generalizable to other types of stem cells.

Stem cell therapies work by promoting endogenous repair; that is, they aid damaged tissue in repairing itself by secreting “paracrine factors,” including proteins and genetic materials. While stem cell therapies can be effective, they are also associated with some risks of both tumor growth and immune rejection. Also, the cells themselves are very fragile, requiring careful storage and a multi-step process of typing and characterization before they can be used.

Ke Cheng, associate professor of molecular biomedical sciences at NC State University, associate professor in the joint biomedical engineering program at NC State and UNC and adjunct associate professor at the UNC Eshelman School of Pharmacy, led a team in developing the synthetic version of a cardiac stem cell that could be used in off-the-shelf applications.

Cheng and his colleagues fabricated a cell-mimicking microparticle (CMMP) from poly (lactic-co-glycolic acid) or PLGA, a biodegradable and biocompatible polymer. The researchers then harvested growth factor proteins from cultured human cardiac stem cells and added them to the PLGA. Finally, they coated the particle with cardiac stem cell membrane.

“We took the cargo and the shell of the stem cell and packaged it into a biodegradable particle,” Cheng says.

When tested in vitro, both the CMMP and cardiac stem cell promoted the growth of cardiac muscle cells. They also tested the CMMP in a mouse model with myocardial infarction, and found that its ability to bind to cardiac tissue and promote growth after a heart attack was comparable to that of cardiac stem cells. Due to its structure, CMMP cannot replicate – reducing the risk of tumor formation.

“The synthetic cells operate much the same way a deactivated vaccine works,” Cheng says. “Their membranes allow them to bypass the immune response, bind to cardiac tissue, release the growth factors and generate repair, but they cannot amplify by themselves. So you get the benefits of stem cell therapy without risks.”

The synthetic stem cells are much more durable than human stem cells, and can tolerate harsh freezing and thawing. They also don’t have to be derived from the patient’s own cells. And the manufacturing process can be used with any type of stem cell.

“We are hoping that this may be a first step toward a truly off-the-shelf stem cell product that would enable people to receive beneficial stem cell therapies when they’re needed, without costly delays,” Cheng says.

Rare Obesity Syndrome Therapeutic Target Identified

Columbia University Medical Center (CUMC) researchers have discovered that a deficiency of the enzyme prohormone covertase (PC1) in the brain is linked to most of the neuro-hormonal abnormalities in Prader-Willi syndrome, a genetic condition that causes extreme hunger and severe obesity beginning in childhood. The discovery provides insight into the molecular mechanisms underlying the syndrome and highlights a novel target for drug therapy.

The findings were published online today in the Journal of Clinical Investigation.

“While we’ve known for some time which genes are implicated in Prader-Willi syndrome, it has not been clear how those mutations actually trigger the disease,” said lead author Lisa C. Burnett, PhD, a post-doctoral research scientist in pediatrics at CUMC. “Now that we have found a key link between these mutations and the syndrome’s major hormonal features, we can begin to search for new, more precisely targeted therapies.”

An estimated one in 15,000 people have Prader-Willi syndrome (PWS). The syndrome is caused by abnormalities in a small region of chromosome 15, which leads to dysfunction in the hypothalamus—which contains cells that regulate hunger and satiety—and other regions of the brain. A defining characteristic of PWS is insatiable hunger. People with PWS typically have extreme obesity, reduced growth hormone and insulin levels, excessive levels of ghrelin (a hormone that triggers hunger), and developmental disabilities. There is no cure and few effective treatments for PWS.

Dr. Burnett and her colleagues used stem cell techniques to convert skin cells from PWS patients and unaffected controls into brain cells. Analysis of the stem cell-derived neurons revealed significantly reduced levels of PC1 in the patients’ cells, compared to the controls. The cells from PWS patients also had abnormally low levels of a protein, NHLH2, which is made by NHLH2, a gene that also helps to produce PC1.

To confirm whether PC1 deficiency plays a role in PWS, the researchers examined transgenic mice that do not express Snord116, a gene that is deleted in the region of chromosome 15 that is associated with PWS. The mice were found to be deficient in NHLH2 and PC1 and displayed most of the hormone-related abnormalities seen in PWS, according to study leader Rudolph L. Leibel, MD, professor of pediatrics and medicine and co-director of the Naomi Berrie Diabetes Center at CUMC.

“The findings strongly suggest that PC1 is a good therapeutic target for PWS,” said Dr. Burnett. “There doesn’t seem to be anything wrong with the gene that makes PC1—it’s just not getting activated properly. If we could elevate levels of PC1 using drugs, we might be able to alleviate some of the symptoms of the syndrome.”

“This is an outstanding example how research on human stem cells can lead to novel insight into a disease and provide a platform for the testing of new therapies,” said Dieter Egli, PhD, a stem cell scientist who is an assistant professor of developmental cell biology (in Pediatrics) and a senior author on the paper.

“This study changes how we think about this devastating disorder,” said Theresa Strong, PhD, chair of the scientific advisory board of the Foundation for Prader-Willi Research and the mother of a child with PWS. “The symptoms of PWS have been very confusing and hard to reconcile. Now that we have an explanation for the wide array of symptoms, we can move forward with developing a drug that addresses their underlying cause, instead of treating each symptom individually.”

Following the findings reported in this paper, the Columbia research team began collaborating with Levo Therapeutics, a PWS-focused biotechnology company, to translate the current research into therapeutics.

JCyte Completes Enrollment For Phase I/IIa Safety Trial

Company is poised to begin phase IIb efficacy trial in 2017

California-based regenerative medicine company jCyte has completed enrollment in a phase I/IIa trial to study the safety of its stem cell therapy candidate for retinitis pigmentosa (RP). The trial included 28 patients with advanced RP, eight of whom have completed the one-year study. Early safety results have been promising.

“We have successfully completed four DSMB (Data Safety Monitoring Board) reviews,” said jCyte co-founder Henry Klassen, MD, PhD. “So far, trial participants have had no significant side effects, with good tolerance of the injected cells. We are quite gratified by the results.”

The company’s investigational therapy, called jCell, uses injected retinal progenitor cells, which are intended to rescue dying retinal cells (rods and cones) and possibly regenerate new ones. The non-surgical treatment requires a single intravitreal injection, which can be performed in an ophthalmologist’s office under local anesthesia.

Retinitis pigmentosa is an incurable eye disease that destroys retinal cells and ultimately leads to blindness. It is a genetic condition that generally strikes people in their teens. Many patients are blind by the time they are 40. Worldwide, almost 1.5 million people suffer from RP, making it the leading cause of inherited blindness. Currently, there are no effective treatments.

The ongoing trial is being conducted at the Gavin Herbert Eye Institute at the University of California, Irvine and Retina Vitreous Associates in Los Angeles and has received significant support from the California Institute for Regenerative Medicine (CIRM).

As the safety trial winds up, jCyte has begun planning a phase IIb trial, which they hope to begin in 2017.

“I look forward to the next stage of development towards commercialization,” says jCyte CEO Paul Bresge. “We never lose sight of our singular goal: to ultimately deliver this much-needed therapy to patients.”

Bresge encourages RP patients who wish to participate in future trials to visit http://www.jcyte.com.

Breakthrough in Understanding How Stem Cells Become Specialized

Scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) have made a major advance in understanding how the cells of an organism, which all contain the same genetic information, come to be so diverse. A study published today in Molecular Cell shows that a protein called OCT4 narrows down the range of cell types that stem cells can become. The findings could impact efforts to produce specific types of cells for future therapies to treat a broad range of diseases, as well as aid the understanding of which cells are affected by drugs that influence cell specialization.

“We found that the stem cell-specific protein OCT4 primes certain genes that, when activated, cause the cell to differentiate, or become more specialized,” said Laszlo Nagy, M.D., Ph.D., professor and director of the Genomic Control of Metabolism Program and senior author of the study. “This priming customizes stem cells’ responses to signals that induce differentiation and makes the underlying genetic process more efficient.”

Differentiation matters
As an organism—such as a human—develops from its simplest, earliest form into maturity, its cells transition from a highly flexible state—stem cells—to more specialized types that make up its tissues. Many labs are trying to recapitulate this process to generate specific types of cells that could be transplanted into patients to treat disease. For example, pancreatic beta cells could treat diabetes, and neurons that produce dopamine could treat Parkinson’s.

What OCT4 does
OCT4 is a transcription factor—a protein that regulates gene activity—that maintains stem cells’ ability to give rise to any tissue in the body. OCT4 works by sitting on DNA and recruiting factors that either help initiate or repress the reading of specific genes.

The new study shows that, at certain genes, OCT4 also collaborates with transcription factors that are activated by external signals, such as the retinoic acid (vitamin A) receptor (RAR) and beta-catenin, to turn on their respective genes. Vitamin A converts stem cells to neuronal precursors, and activation of beta-catenin by Wnt can either support pluripotency or promote non-neural differentiation, depending on what other signals are present. Recruitment of these factors ‘primes’ a subset of the genes that the signal-responsive factors can activate.

The big picture
“Our findings suggest a general principle for how the same differentiation signal induces distinct transitions in various types of cells,” added Nagy. “Whereas in stem cells, OCT4 recruits the RAR to neuronal genes, in bone marrow cells, another transcription factor would recruit RAR to genes for the granulocyte program. Which factors determine the effects of differentiation signals in bone marrow cells—and other cell types—remains to be determined.”

Next steps
“In a sense, we’ve found the code for stem cells that links the input—signals like vitamin A and Wnt—to the output—cell type,” said Nagy. “Now we plan to explore whether other transcription factors behave similarly to OCT4—that is, to find the code in more mature cell types.

“If other factors also have this dual function—both maintaining the current state and priming certain genes to respond to external signals—that would answer a key question in developmental biology and advance the field of stem cell research.”

Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit medical research organization that conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. SBP focuses its research on cancer, immunity, neurodegeneration, metabolic disorders and rare children’s diseases. The Institute invests in talent, technology and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients.

Four NCI Cancer Centers Announce Landmark Research Consortium and Collaborations with Celgene

The Abramson Cancer Center at the University of Pennsylvania, The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai announced the establishment of a research consortium focused on accelerating the discovery and development of novel cancer therapeutics and diagnostics for the benefit of patients.

The consortium aligns four major academic institutions in a unified partnership with the shared goal of creating high-impact research programs to discover new treatments for cancer. The magnitude of the multi-institutional consortium and agreements between Celgene Corporation (NASDAQ: CELG) and each institution will support the rapid delivery of disease-altering programs to the clinic that may ultimately benefit cancer patients, global healthcare systems and society.
Subsequent to establishing the consortium, Celgene entered into four public-private collaboration agreements in which it paid a total of $50 million, $12.5 million to each institution, for the option to enter into future agreements to develop and commercialize novel cancer therapeutics arising from the consortium’s efforts. Over the next ten years the institutions intend to present multiple high-impact research programs to Celgene with the goal of developing new life-saving therapeutics. Subject to Celgene’s decision to opt-in and license the resulting technologies, each program has the potential to be valued at hundreds of millions of dollars.
The four cancer center directors, Steven Burakoff, M.D., of the Icahn School of Medicine at Mount Sinai, Stephen G. Emerson, M.D., Ph.D., of Columbia University, William Nelson, M.D., Ph.D., of Johns Hopkins University and Chi Van Dang, M.D., Ph.D., of the University of Pennsylvania, said in a shared statement, “The active and coordinated engagement, creative thinking and unique perspectives and expertise of each institution have made this collaboration a reality. Our shared vision and unified approach to biomedical research, discovery and development, combined with Celgene’s vast research, development and global commercial expertise, will enable us to accelerate the development and delivery of next-generation cancer therapies to patients worldwide.”

In addition to the benefits of long-standing professional relationships among the four cancer center directors, the depth and breadth of the institutions’ combined research and clinical infrastructures provide an exceptional foundation upon which to build this transformative collaboration. The four institutions collectively care for more than 30,000 new cancer patients each year, and have nearly 800 faculty members who are active in basic and clinical research, and clinical care.

“This is a paradigm-shifting collaboration that further strengthens our innovative ecosystem,” said Bob Hugin, Executive Chairman of Celgene Corporation. “We remain firmly committed to driving critical advances in cancer and believe the tremendous expertise of our collaboration partner institutions will be invaluable in identifying new therapies for cancer patients.”
The four consortium members are among the 69 institutions designated as Cancer Centers by the National Cancer Institute (NCI). These 69 institutions serve as the backbone of NCI’s research in the war against cancer.
The Cancer Trust, a non-profit organization, brought together the four institutions, thereby establishing the multi-institutional research consortium. T.R. Winston & Company, LLC served as the strategic advisor to The Cancer Trust and facilitated negotiations among The Cancer Trust, the institutions and Celgene. The commercialization offices of the four institutions, Columbia Technology Ventures, Johns Hopkins Technology Ventures, Mount Sinai Innovation Partners and the Penn Center for Innovation, subsequently collaborated with Celgene to accelerate this effort to discover and develop new therapies for the treatment of cancer.

“We are extremely proud of what we’ve collectively accomplished through establishing this collaboration and aligning all participants,” said Erik Lium, Ph.D., Senior Vice President of Mount Sinai Innovation Partners. “We look forward to continuing to work closely with one another, our colleagues in research and clinical care, and now with Celgene to advance the discovery of new therapies that will dramatically improve the lives of patients worldwide.”