Emory/UGA Flu Center Is One of Six Centers Leading National H1N1 Research Response

In a multi-pronged attack against the H1N1 virus, researchers at Emory University are using a new method of rapidly producing highly targeted monoclonal antibodies to develop a diagnostic test as well as a temporary therapy to stave off the H1N1 (swine flu) virus. The antibodies, which can be isolated from a small amount of the blood of humans infected with the virus, could be targeted against H1N1 and rapidly reproduced to detect or attack the virus. The monoclonal antibody technology was described last April in the journal Nature and is being developed in collaboration with scientists at the University of Chicago.

In addition, Emory scientists, along with colleagues at the Centers for Disease Control and Prevention (CDC), are using virus-like particles (VLPs) to develop a quicker, more efficient alternative to the current method of making flu vaccine by growing it in chicken eggs. VLPs are empty shells that look like viruses but don’t reproduce. In March, the scientists described the effectiveness of their VLP vaccine in mice in the journal PLoS (Public Library of Science) One.

An Emory-University of Georgia Influenza Pathogenesis and Immunology Research Center (IPIRC) is a key component in a national scientific effort to address the H1N1 (swine flu) outbreak. The intensive U.S. research initiative, led by the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), is centered in six national NIH Centers of Excellence for Influenza Research and Surveillance, including the one led by Emory University and UGA.

“Emory has one of the world’s leading groups of infectious disease experts, vaccine scientists, immunologists and microbiologists,” says David S. Stephens, MD, vice president for research in Emory’s Woodruff Health Sciences Center. “Our research and groundbreaking discoveries by scientists at the Emory Vaccine Center, the Yerkes National Primate Research Center, Emory University School of Medicine and collaborators at the University of Georgia provide a strong basis for our contribution to this coordinated national effort against H1N1.”

Emory scientists in the flu research center are conducting several key projects as part of the national research effort. These include determining how the H1N1 virus enters cells, is transmitted, and how that process might be interrupted; finding out whether prior exposure to other influenza viruses may help or hinder immune responses to the new virus; assessing possible pre-existing immunity to H1N1 in different age groups; analyzing the recovery of infected patients; developing a method to quickly make monoclonal antibodies targeted to the H1N1 virus; and beginning the initial stages of a new vaccine.

At the University of Georgia, scientists are studying how the H1N1 virus is transmitted between animals; finding out how the virus infects human airway cells; developing diagnostic tests to distinguish different virus strains; evaluating the stability of the virus; and testing vaccines and anti-viral drugs against the virus.

“Our scientific team is proud to be contributing to the public good as one of the six influenza research centers in the U.S.,” says Richard Compans, PhD, director of the Emory-UGA center. “The pairing of Emory's expertise with strengths at UGA in animal pathology creates a uniquely effective combination for studying crossover viruses such as 'swine flu.’ We expect to make significant contributions to this national research effort.”

The Emory-UGA IPIRC, along with the five other national flu centers, was established in April 2007 with a seven-year, $32.8 million contract from the NIH.

In the event of a public health emergency involving the emergence and spread of an influenza pandemic in humans, the network of centers is directed to “be on the frontline” to implement the NIAID Pandemic Public Health Research Response Plan.

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Mayo Clinic Researchers find Adding Epratuzumab to Standard Therapy for Aggressive Lymphoma Produces Significant Overall Response

mdash - Adding a second monoclonal antibody drug to chemotherapy looks promising for treatment of diffuse large B-cell lymphoma, according to Mayo Clinic researchers working with the North Central Cancer Treatment Group (NCCTG) (http://ncctg.mayo.edu/). Results of this interim analysis were released May 15 as part of the 44th Annual Meeting of the American Society of Clinical Oncology.

Researchers found that 95 percent of patients responded to treatment that included the drug epratuzumab with the standard "R-CHOP" therapy. R-CHOP combines three chemotherapy drugs (cyclophosphamide, doxorubicin and vincristine) with the steroid drug prednisone and rituximab, a monoclonal antibody. Final results will be reported next year.

Diffuse large B-cell lymphoma is one of the most common and aggressive forms of non-Hodgkin lymphoma (NHL), a cancer of the white blood cells known as B-lymphocytes.

In 78 patients, researchers found:
• 95 percent of participants (75 patients) improved as a result of the treatment.
• 63 percent of participants (47 patients) were disease free.

Researchers also were able to look at the primary endpoint of the study — disease-free survival at 12 months — in 34 patients. Eighty five percent of that group, 29 patients, had no signs of lymphoma.

"These results are good, but whether it will turn out to be better than standard therapy is still unknown," says the study's lead author, Ivana Micallef, M.D. (http://mayoresearch.mayo.edu/mayo/research/staff/micallef_in.cfm), a Mayo Clinic hematologist.

Epratuzumab is much like rituximab because both are monoclonal antibodies, and both attach to proteins commonly found on the surface of B-cells — CD20 for rituximab and CD22 for epratuzumab. Both also are used to treat certain autoimmune disorders, such as rheumatoid arthritis and lupus. "In autoimmune disease, you are trying to stop the B-cells from making the antibodies that cause inflammation, but in cancer, these B-cells are malignant," says Dr. Micallef.

This is the first large study to combine epratuzumab with chemotherapy, in this case R-CHOP.
The rate of toxic side effects among enrolled patients was the same as seen in R-CHOP use, investigators say. "Overall, the combination was well tolerated," says Dr. Micallef. Patients may experience low blood counts, fatigue or infections.

As promising as these results look, researchers will not know if this new treatment provides superior results to R-CHOP unless the two regimens are compared with each other, she says.

Other NCCTG collaborators included Matthew Maurer, Paul Kurtin, M.D., and Thomas Witzig, M.D., all of Mayo Clinic; Daniel Nikcevich, M.D., St. Mary's Duluth Clinic, Duluth, Minn.; Michael Cannon and Dennis Moore, M.D., both of Cancer Center of Kansas PA, Wichita.

NCCTG is a national clinical research group sponsored by the National Cancer Institute. Its research and administration are based at Mayo Clinic. NCCTG consists of a network of cancer specialists at community clinics, hospitals and medical centers in the United States, Canada and Mexico. The group is dedicated to bringing clinical trials with promising new cancer therapies to communities where patients live.