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Hutchinson Center to lead a $20 million research project to explore a potential cure for HIV infection

Five-year federally funded study will test transplantation of gene-modified cells

SEATTLE - July 11, 2011 - Whether a stem cell transplant using an HIV-infected person's own genetically modified immune cells can become a cure for the disease is the focus of a new $20 million, five-year research grant award announced today by the National Institutes of Health to Fred Hutchinson Cancer Research Center.

Hutchinson Center researchers will use the grant to lead a multifaceted team of scientists and institutions to study whether a person's own stem cells can be engineered to deny HIV entry into the body's blood cells. The researchers also will work to develop tools to eradicate existing reservoirs of infection in the body.

"Funding for research to find a cure for HIV-infected persons represents a paradigm shift," said Keith Jerome, M.D., Ph.D., an expert in viral infections and co-principal investigator of the grant. "HIV has been an incurable, lifelong infection that at best sentences people to a lifetime of complex drug therapies. Now the research field is shifting to address the possibility of a cure. No one would have talked about this approach five years ago."

Jerome is an associate member of the Hutchinson Center's Vaccine and Infectious Disease Division. The other co-principal investigator is stem cell transplant researcher Hans-Peter Kiem, M.D., a member of the Hutchinson Center's Clinical Research Division and recipient of the Center's Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research.

"I am particularly excited that we can explore stem cell-based therapies for the cure of HIV," Kiem said. "It is a perfect fit for our institution, which has such a unique history of pioneering stem cell transplantation and research in HIV ."

The Hutchinson Center grant was one of three announced today by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, to fund research focused on developing strategies for eradicating HIV infection via its Martin Delaney Collaboratory program.

"I applaud the NIAID's efforts to open up new areas of research funding to find a potential cure for HIV," said Larry Corey, M.D., president and director of the Hutchinson Center. "The work to be done in this grant is groundbreaking and the kind of public/private collaboration that is needed to move the science forward."

The research projects will focus on ways around a major obstacle to long-term control and cure of HIV: the persistence of HIV provirus in reservoirs throughout the bodies of infected persons. The infected cells in these reservoirs are long lived and remain a threat during the lifespan of infected persons. Highly active antiretroviral therapy (HAART), although successful at keeping the spread of HIV under control by inhibiting viral replication, does not eliminate these reservoirs. If a patient discontinues HAART, the virus rebounds.

One approach under investigation is autologous stem cell transplantation, in which the infected patient's own immune cells are genetically modified to be resistant to HIV by eliminating one of the receptors, called CCR5, which HIV needs to infect new cells. This method builds on the Hutchinson Center's long-standing expertise in using transplantation to treat and cure blood cancers and some autoimmune diseases, a Nobel Prize-winning accomplishment that has boosted survival rates from nearly zero to 90 percent for certain types of leukemia.

Stem cell transplantation to eliminate HIV infection has one intriguing precedent. In 2008, a group of German physicians published results of transplanting an American man who had acute myeloid leukemia and HIV. The so-called "Berlin patient" received a new immune system from donor cells that also carried a rare genetic variation that made them resistant to HIV. The man was able to stop HAART and the virus remained undetectable. However, few stem cell donors have this genetic mutation, so a way must be found to modify the patient's own immune cells to be HIV resistant in order for such a transplant to be more widely available.

A second approach to be studied involves developing DNA-targeting proteins to directly attack the reservoirs of HIV provirus without harming the infected cells themselves. This method would complement the stem cell-based approach and could potentially lead to elimination of the HIV provirus.

In addition to better understanding the biology and virology of gene-modified cells, another goal will be to optimize the combination of stem cell protection and HIV reservoir-purging techniques. Researchers expect to have enough data to begin human clinical trials in five years.

The team of scientists and institutions that will conduct the studies includes Sangamo Biosciences of Richmond, Calif., Beckman Research Institute at City of Hope in Duarte, Calif., the University of Washington and Seattle Children's.

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Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit www.fhcrc.org .

MEDIA CONTACT
Dean Forbes
Fred Hutchinson Cancer Research Center
(206) 667-2896
dforbes@fhcrc.org

 

Source: Fred Hutchinson Cancer Research Center

"Reproduced with permission - Fred Hutchinson Cancer Research Center "

Fred Hutchinson Cancer Research Center
fhcrc.org


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