Marching Orders

Marching orders

Emory aims to be command central in the fight against autoimmune disease

By Dana Goldman  |  Illustrations by Camille Chisholm

Jacques Galipeau likens what he does to taking a few cells and turning them into an army of combat soldiers—soldiers that he hopes will win the war against Crohn’s and other autoimmune diseases.

These “soldiers” are the result of a “cellular bootcamp,” a technique Galipeau is perfecting here at Emory that offers patients a chance to use their own cells to fight off the often debilitating symptoms of autoimmune disease. Galipeau, a French Canadian scientist internationally known for putting multiple sclerosis in remission in mice by suppressing their immune system, came to Emory in 2009 with one tactical mission in mind, to set up the Emory Personalized Immunotherapy Center, or EPIC.

Ian Copeland and Jacques Galipeau

EPIC is grounded in research by Galipeau and others showing that a particular type of cell in bone marrow called mesenchymal stromal cells can be useful in fighting autoimmune diseases like Crohn’s. As Galipeau explains, “The cells nest in your marrow and do a really important job in promoting blood cell development and also in regulating the immune response and participating in wound repair.”

EPIC’s lab director, Ian Copland, has been working with mesenchymal stromal cells since 2005, when he joined Galipeau’s lab in Montreal as a postdoctoral fellow. “This rare population of cells has the ability to modulate the body’s immune response,” says Copland. “Mesenchymal cells have the unique ability to sense their environment and respond accordingly. If there’s no reason for them to be activated, they don’t do anything.” Unlike many treatments for autoimmune diseases, personalized cell therapy with mesenchymal stromal cells won’t attack systems that are working correctly. As an added bonus, using a patient’s own cells significantly decreases the likelihood that the body would reject the cells.

Still, there’s a reason that use of these cells remains experimental, says Galipeau. “Mesenchymal stromal cells are very rare. For every 100,000 cells in your bone marrow, there’s one mesenchymal stromal cell. It’s been difficult to take advantage of their special abilities when they typically exist in the human body in such small numbers. The key to success will be to reliably produce ‘personalized’ mesenchymal cells in numbers that will be useful for treatment.”

Mass-producing mesenchymal cells

Galipeau and Copland have come a long way in addressing the issue of producing mesenchymal cells in large numbers. Their first clinical trial, expected to start this year, will focus on young adults with Crohn’s disease. A few tablespoons of a patient’s bone marrow will be extracted in an outpatient procedure. The patient’s mesenchymal stromal cells will be separated out. “We can fill up whole stacks of tissue culture plates of these cells because they have intrinsic properties that make them start growing like weeds when we put them in a special growth medium,” says Galipeau.

That special growth medium is unique to EPIC. “The vast majority of studies using cells that were expanded in the laboratory have used culture broth that incorporates cow blood extracts,” says Copland. “We have developed a method using platelets from which we derive an entirely human protein extract. The extract allows for production of cells without use of bovine or other non-human growth factors.”

In addition, Galipeau’s team diverges from other studies in another important way. A few years ago, Galipeau realized that cells that were frozen and then thawed right before transfusion into patients were less effective than fresh cells. “We believe that giving live cells, though more labor intensive, will be much more potent than giving their thawed counterpart, which is more practical but possibly less effective,” says Galipeau.  “In our mind, cells are like sushi: fresh is best.” 

After a few weeks, doctors will harvest the resulting large crop of mesenchymal stromal cells and return them to the patient’s body through a blood transfusion. “The pharmacological effect of receiving this very large dose of your own immune soldiers is that they hose down inappropriate autoimmune response,” while leaving the appropriate immune response intact, says Galipeau. 

Traditional drugs used to suppress parts of the immune system generally end up impacting the entire immune system. With drugs like cortisone, says Galipeau, “you’re susceptible to complications that arise from a suppressed immune system.” Depending on the autoimmune disease, patients may need one transfusion or repeated transfusions of mesenchymal stromal cells over time. Future studies at EPIC will focus on the optimal number, and eventually, Galipeau hopes, on diseases other than Crohn’s, including graft-versus-host disease, lupus, and multiple sclerosis.

A resource for researchers far and wide 

  The key

The work of growing and harvesting the cells will happen at EPIC’s core facility on the sixth floor of Emory University Hospital. This facility is largely the work of Copland, who serves with Galipeau as a sort of co-captain for the EPIC team. A year after Galipeau came to Emory from Canada, Copland followed, drawn by Galipeau’s vision for EPIC and ready to put the lab and its clinical trials together from the ground up. He oversaw the design and construction of EPIC’s lab space in the hospital’s blood bank, including a 350-square-foot, class-10,000 positive-pressure clean room (exists no more than 10,000 particles larger than 0.5 microns per cubic foot of air) to ensure good quality control.

Says Galipeau, “There are virtually no other facilities in Georgia accessible to university researchers that will allow scientists to manufacture cells for personalized therapy and to test these as part of FDA-regulated innovative clinical trials. At this point, our research is meant strictly to enhance understanding of a technological platform which may have tremendous benefit, but is not ‘owned’ by anybody.” EPIC’s support is coming from Emory’s School of Medicine and Children’s Healthcare of Atlanta, with plans to apply for state and federal funds in the future.

Copland is hoping the facility stays busy not just with his team’s research but also with the immunotherapy work of other scientists. He and Galipeau are viewing EPIC as a university and community resource for researchers who otherwise would have to turn to industry or stop altogether. Says Copland, “Usually promising academic research withers on the vine because it requires a huge investment to manufacture products like these in good conditions to allow for first-in-human studies. People start to look at the hurdles, and it never happens. The EPIC program will help get past that barrier from the bench to the bedside.” 

The team has begun collaborating with scientists not just at Emory but also at Georgia Tech, University of Georgia, and Georgia State University.

Within a few years, Galipeau hopes, he’ll have study results showing the effectiveness of the mesenchymal stromal cells in patients, young and old, dealing with a range of ailments related to the immune system. Then he wants to expand EPIC’s efforts into a different cellular platform. Other cells, like B-regulatory cells, show potential too if put in the right cellular boot camp. He thinks that advances at EPIC could lead to cellular therapy for not just immune system disorders but also infectious diseases and cancer. “And the vision is that we here at Emory would become the national go-to place for personalized cell therapies,” says Galipeau. “It’s just a question of lining up the ducks, bringing in the right people, and pushing the envelope. That’s the fun part.”  EM

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