Researchers on Sunday reported that they genetically engineered immune cells that can detect HIV even when it tries to disguise itself, potentially suggesting a new way to treat HIV infection. Engineered versions of cytotoxic T lymphocytes (CTLs), also known as CD8 killer T cells, were able to recognize other cells infected by HIV and slow HIV’s spread in lab dishes.
“Billions of these anti-HIV warriors can be generated in two weeks,” said study co-leader Angel Varela-Rohena of the University of Pennsylvania.
HIV not only attacks CD4 immune cells that help mount the body’s defense: The virus also can disguise itself from CTLs by hiding a protein called HLA-I-associated antigen. “CTLs are crucial for the control of HIV infection,” the researchers wrote. “Unfortunately, HIV has an arsenal of mutational and nonmutational strategies that aid it in escaping from the CTL response mounted against it by its host.”
To counter this, Varela-Rohena and colleagues took CTLs from an HIV patient and genetically engineered them to detect HIV that had escaped natural T cells. “It is possible to improve on nature when it comes to preventing HIV CTL escape,” the scientists wrote. In addition, “the engineered T cells responded in a much more vigorous fashion so that far fewer T cells were required to control infection,” said James Riley, a study co-author at the University of Pennsylvania.
“In the face of our engineered assassin cells, the virus will either die or be forced to change its disguises again,” said co-author Andy Sewell of Britain’s Cardiff University, a step the researchers hope will further weaken the virus. The researchers plan to begin testing the treatment in HIV patients in 2009.
“We have managed to engineer a receptor that is able to detect HIV’s key fingerprints and is able to clear HIV infection in the laboratory,” said Bent Jakobsen, chief scientific officer at Adaptimmune Ltd., the British firm that owns the technology.
The full report, “Control of HIV-1 Immune Escape by CD8 T Cells Expressing Enhanced T-Cell Receptor,” was published ahead of print by Nature Medicine online (2008;doi:10.1038/nm.1779).
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