Rachael A. Clark, MD, PhD, BWH assistant professor of dermatology and associate dermatologist and Thomas Kupper, MD, BWH Department of Dermatology chairman and their colleagues now report a new study that low-dose Campath (alemtuzumab) not only treats patients with L-CTCL but does so without increasing their risk of infections.
The study was electronically published on January 18, 2012 in Science Translational Medicine.
Campath was previously believed to kill all lymphocytes (T-cells and B-cells) in the body and render patients susceptible to infections. However, Clark and Kupper found that Campath only kills T-cells that enter the bloodstream, but it spares a newly discovered population of T-cells that live long-term in the tissues.
"We noticed that our patients were not getting infections, and we looked in the skin. We saw healthy T-cells remaining there despite the fact that there were no T-cells in the blood," said Clark. "We used to believe that most T-cells responsible for protecting against infection were in the bloodstream. But we now realize that highly protective T-cells also inhabit tissues such as the skin, lungs and gastrointestinal tract. It is these tissue resident T-cells that are critical in protecting us from infection on a day-to-day basis."
By showing that Campath kills circulating T-cells, including the cancerous T-cells, but spares tissue resident T-cells, Clark and Kupper have shown that Campath effectively treats L-CTCL while sparing normal immunity. Their findings are also the first demonstration in human beings that tissue resident T-cells provide frontline immune protection of the skin.
"We're very grateful to our patients for entrusting us with their care and for teaching us important lessons about the immune system." said Clark.
In a companion piece, Mark Davis, PhD, Stanford University School of Medicine, called the work a "translational tour de force."
This research was funded by the National Institutes of Health, the Damon Runyon Cancer Research Foundation, the Leukemia & Lymphoma Society, the Foundation Rene Touraine and a charitable contribution from Edward P. Lawrence, Esq.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), www.brighamandwomens.org/research, BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit www.brighamandwomens.org.
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