Hutch News

Jerome, Kiem lead $20 million study to cure HIV

Five-year, federally funded research will test transplantation of gene-modified immune cells

July 11, 2011
Drs. Keith Jerome (left) and Hans-Peter Kiem

Drs. Keith Jerome (left) and Hans-Peter Kiem will lead studies of stem cell-based therapies for the cure of HIV.

Center News file photos

Can a stem cell transplant using an HIV-infected person’s own genetically modified immune cells cure the person of the disease? Armed with a $20 million, five-year research award from the National Institute of Allergy and Infectious Diseases, Hutchinson Center researchers intend to find out.

Drs. Keith Jerome and Hans-Peter Kiem 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 scientists also will work to develop tools to eradicate existing reservoirs of infection in the body.

A ‘paradigm shift’ toward a cure

“Funding for research to find a cure for HIV-infected persons represents a paradigm shift,” said Jerome, co-principal investigator of the grant. Jerome is an expert in viral infections in the Center's Vaccine and Infectious Disease Division and an associate professor in Laboratory Medicine at the University of Washington. “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,” he said.

“I am particularly excited that we can explore stem cell-based therapies for the cure of HIV,” said co-principal investigator Kiem, a stem cell transplant researcher in the Clinical Research Division and recipient of the Center’s Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research. “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 just announced by the NIAID, 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 Dr. Larry Corey, Center president and director. “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.”    

Eradicating reservoirs of infection

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. 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.

Among the research approaches the team will investigate:

  • Autologous stem cell transplantation—In this approach, 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.
  • Development of DNA-targeting proteins—These proteins 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.

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 researchers  must find a way to modify a patient’s own immune cells to be HIV resistant.
     
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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