Researchers at the University of Pennsylvania School of Medicine and colleagues in the United Kingdom have engineered T cells able to recognize HIV-1 strains that have evaded the immune system.
The findings of the study, published online in the journal Nature Medicine, have important implications for developing new treatments for HIV, especially for patients with chronic infection who fail to respond to antiretroviral regimens.
When viruses enter the body, they hijack the machinery of host cells to replicate and spread infection. When the body's cells are infected with a virus they expose small parts of the virus on their surface, offering a molecular fingerprint called an epitope for killer T-cells from the immune system to see. This triggers an immune response, eliminating the virus and any cells involved in its production. However, HIV has the ability to mutate quickly, swiftly disguising its fingerprints to allow it to hide from killer T-cells.
Natural T cells recognize their targets through weak molecular interactions mediated by the T cell receptor. Through a clever molecular process, the investigators were able to isolate a group of T cell receptor encoding genes that bind to HIV-1 about 450-fold more strongly.
"Not only could T cells engineered to express the strongly binding T cell receptor see HIV strains that had escaped detection by natural T cells, but the engineered T cells responded in a much more vigorous fashion so that far fewer T cells were required to control infection," says co-senior author James Riley, PhD, Research Associate Professor of Pathology and Laboratory Medicine at Penn.
What's more, adds first author Angel Varela-Rohena, PhD, who recently completed these studies as part of his PhD dissertation, "With the present availability of potent systems to replicate and deliver high-affinity HIV-1 specific T-cell receptors, billions of these anti-HIV-1 warriors can be generated in two weeks."