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Closing The Gap Between Lab and Clinicby Ruth SoRelle, MP.H. 
Drs. Cliona Rooney (left) and Helen Heslop have pooled their expertise and talents to come up with groundbreaking treatments to fight cancer. Translational medicine is today's biomedical buzzword, but two Baylor College of Medicine researchers made it a reality before it even had a name. For more than a decade, Dr. Cliona Rooney, professor of pediatrics at BCM, and Dr. Helen Heslop, professor of pediatrics and medicine at BCM, have pooled their expertise and talents to come up with groundbreaking treatments that manipulate the ability of immune system cells to fight cancers. Rooney, a bench scientist, and Heslop, a physician with roots in the laboratory, are both members of the faculty of the Center for Cell and Gene Therapy, a joint program of BCM, The Methodist Hospital and Texas Children's Hospital. Their partnership began in the early 1990s, at St. Jude's Children's Research Hospital in Memphis, Tenn., when they helped pioneer a treatment for a complication occurring with bone marrow transplants that were not perfect matches for cancer patients. To prevent potentially fatal graft-versus-host disease, the transplant team removed immune components called T-cells from the marrow. This reduced the likelihood that the immune cells in the graft would attack the tissues of the immune-deficient patients. However, it also left the patients prey to viruses. One—Epstein-Barr virus (EBV)—caused almost invariably fatal lymphomas. To solve this, Heslop and Rooney gave patients infusions of specially grown T-cells that only attacked Epstein-Barr virus. They found that if patients got these before lymphoma appeared, it prevented the lymph cancer. In five of six patients who already had lymphoma, the T-cells successfully fought the cancer. The research evolved after a move to BCM in 1997 with the Center for Cell and Gene Therapy director Dr. Malcolm Brenner. The team next targeted wily tumors of the nasal passages and pharynx and a lymph system disease called Hodgkin's—both associated with Epstein-Barr virus. In Hodgkin's and nasopharyngeal cancer, the tumor brings in protective "bystander" cells that inhibit the T-cells from attacking the malignancy. In initial studies with the same type of T-cells used previously, the treatment worked in about one-third of patients. That was not good enough for the two, and they went back to the laboratory to make T-cells more specific for EBV and are now giving them in conjunction with an antibody to deplete the "bystander cells." A study of this treatment began two years ago, and the results are not yet in. Yet it is a good example of how translational medicine travels from the lab to the clinic and back again. In current laboratory studies, Rooney and Heslop are arming the cells genetically to overcome suppressive substances secreted by the tumor cells. A whole team makes it possible, meeting every Monday to discuss where to go next. "The people who grow the cells know what's happening as do the research nurses. Everyone needs to talk to everyone else," said Heslop. "It's a huge effort that requires different skills." BCM and Texas Children's Hospital's laboratory, where cell and gene therapies for use in people are developed, has been an important part of their success as has been the clinical monitoring of patients to find out what works and what doesn't. The monitoring proved important when they collaborated with Dr. John Goss and his team at Texas Children's who were doing liver transplants in children. The drugs that suppressed the youngster's immune system put them at risk for EBV lymphomas. They tried the T-cells treatment, but what really worked was monitoring the levels of EBV in the patients' blood. When the levels were high, the doctors reduced the immune suppressing drugs. The amount of virus went down and, with it, the risk of lymphoma. "Now they don't need our T-cells any more," said Heslop. Currently, she, Rooney and the team are working to develop T-cells that recognize and attack three common viruses—Epstein-Barr, cytomegalovirus and adenovirus. All three cause serious problems for cancer patients and others with depressed immune systems. The refinements in their treatments depend on a lifeline built from their individual talents, their team and the constant communication between laboratory and clinic that is the epitome of translational medicine. Drs. Rooney and Heslop have pooled their expertise and talents to come up with groundbreaking treatments tofight cancer. |
Patient CareResearchTrekking Into New Territory: Translational Biology and Molecular Medicine Closing the Gap Between Lab and Clinic EducationTulane's Journey Back to New Orleans Community ServiceAlumni & DevelopmentCollege News
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Volume 2, Issue 2, Summer 2006 |
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