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2011 News Releases
Longwood biology professor to continue anti-cancer research from graduate school
November 9, 2011
A Longwood University biology professor is continuing her graduate school research on a novel form of immunotherapy that has shown promise in cancer treatment.
For the last six years, Dr. Amorette Barber, assistant professor of biology, participated in a research project at Dartmouth Medical School where she was enrolled as a doctoral student (2005-09) and in a postdoctoral fellowship (2009-11). The project genetically alters T cells - one of the major types of white blood cells involved in fighting diseases - to form a hybrid immune cell that has been found to recognize and kill tumors in both mice and humans. The research has focused on the hybrid cell's receptor, called a chimeric NKG2D receptor, which recognizes cancer cells and may be able to target tumors selectively.
Barber, an immunology specialist who joined the Longwood faculty this fall semester, will continue this research on her own beginning in the spring semester and will be assisted by students. Three students already have expressed interest in working with her.
"This research is a new way to target cancer cells," she said. "We're combining the best aspects of two kinds of immune cells, T cells and natural killer (NK) cells, into one type of cell that can be used for therapy. This is a fusion of two different and naturally occurring receptors, which usually appear on the outside of a cell and, when activated, send signals to the cell to perform some function. This involves 'adoptive transfer,' in which you take immune cells out of a patient, alter those cells or simply add more of the same cells, then give the cells back to the patient. The chimeric NKG2D receptor - chimeric is the scientific term for hybrid - is what we give to the patient. We have done research on mice, and on human cells in the lab, but not on humans. Clinical trials on humans, which requires approval from the Food and Drug Administration, is the next step."
The principal investigator for the project is Dr. Charles Sentman, associate professor of microbiology and immunology at Dartmouth Medical School, which has Ph.D. students in addition to medical students. Barber joined Sentman's lab in June 2005, nine months after entering the doctoral program. She worked in the lab until graduating in June 2009 with a Ph.D. in molecular and cellular biology, then she worked there two more years in a postdoctoral fellowship.
"There are currently many groups that are doing similar studies and clinical trials with other types of receptors, but the novelty of this research is the specific combination of NKG2D receptors and T cell receptors," Barber said. "This is a unique combination of these two receptors, which activates the T cells differently than similar therapies. The chimeric NKG2D receptor has increased anti-tumor effects due to the fact that the chimeric NKG2D T cells depend on the secretion of cytokines for anti-tumor efficacy."
The research has looked at several types of cancer, including ovarian cancer, myeloma, lymphoma, colon cancer and melanoma. "We've had good results," Barber said. "The research has shown that chimeric NKG2D T cells in mice and humans kill tumor cells and produce proinflammatory cytokines, protein secreted from T cells, which activate an immune response against the tumor. T cells can kill tumors or can make cytokines, either of which is good, and some cells do both. Treatment with chimeric NKG2D T cells leads to longterm, tumor-free survival in mouse models of cancer."
This approach takes advantage of the best cancer-detecting and -fighting qualities of the receptors on both T cells and NK cells, including the latter's ability to recognize stress-induced proteins that appear on many different cancer cells but not on normal cells. NK cells, like T cells, are white blood cells that are part of the body's immune system.
"Sentman and his team believed they could modify the the NKG2D receptor to form a new hybrid immune cell having the power of a T cell and the wide tumor recognition of an NK cell," says an April 2010 news release by the cancer center affiliated with Dartmouth Medical School. "To make the new designer cells, Dr. Sentman removed T cells from the body and reprogrammed them to include modified NKG2D receptors. The hybrid cells were transfused back into the body to start their work. And work they did!...In fact, Sentman found that infusing the hybrid T cells induced a strong immune response that protected mice from the tumor long after the infused T cells were undetectable."
"T cells don't recognize tumors well, so we're essentially giving them a new pair of glasses," Sentman said of the research.
Fortunately, the chimeric NKG2D receptor is "able to kill the tumor cells but leave the healthy tissues alone," Barber said. "Some therapies, such as chemotherapy or radiation, damage healthy tissues."
An article in the Sept. 13 issue of the "Science Times" section of the New York Times detailed similar immunotherapy research by Dr. Carl June, professor of medicine at the University of Pennsylvania School of Medicine, whom Barber knows. Immunology, the story says, "may signify a turning point in the long struggle to develop effective gene therapies against cancer...In essence, the team is using gene therapy to accomplish something that researchers have hoped to do for decades: train a person's immune system to kill cancer cells....Chimeric antigen receptors transform the cells into, in Dr. June's words, 'serial killers.'"
In her postdoctoral fellowship at Dartmouth Medical School, which ended June 30 this year, Barber worked on signaling, one aspect of the research in which she plans to involve Longwood students. "Signaling is studying the messages the receptor sends to the T cell, which is a gray area," she said. "Signaling will be easier to work on than the clinical trials on mice, which is expensive. The lab has had grants from the National Institutes of Health, and now Dr. Sentman is applying for other grants. The research here by students and me will be independent of the project at Dartmouth, though I will maintain collaboration with Dr. Sentman. I want to work side-by-side with students."
"Here at Longwood, I want to study why this receptor is unique and why we have enhanced its efficiency so that it's more efficient than other people's receptors," Barber said. "I want to study the molecular mechanisms of this receptor and to make new, similar receptors using a different set of targeting mechanisms that would target other types of cancer cells. Maybe we can alter other people's mechanisms to make them more efficient. We know that this receptor works; we want to know how it works. If we understand how it works, we can improve it."
Students at Dartmouth Medical School choose the lab in which they want to work after doing "rotations" of 12 weeks each in three different labs. Sentman's lab was Barber's first rotation. Dartmouth Medical School, the fourth oldest (1797) medical school in the United States, is in Lebanon, N.H., two miles from the Dartmouth College campus, which is in Hanover, N.H.
"Dr. Barber's work looked at advanced ovarian cancer patients and myeloma patients," said Sentman, who has studied NK cells for 20 years. "She made a huge contribution and was responsible for some important findings in testing that helped move the project forward. When you're working with animals in the lab, you have to show both the safety and the efficacy of the research before you can do clinical trials on humans, and her work accomplished that."Barber is teaching genetics at Longwood and hopes to start a course on cancer biology. A native of Glens Falls, N.Y., in the Adirondack Mountains, she also is a graduate of the University of Richmond, where she earned a B.S. in biology in 2003.