Researchers at Adaptimmune Limited and the University of Pennsylvania School of Medicine, have announced the approval of an Investigational New Drug (IND) application from the US Food and Drug Administration (FDA) and opening for enrolment of the first ever study using patients’ cells carrying an engineered T cell receptor to treat HIV (SL9 HA-GAG-TCR). The trial may have important implications in the development of new treatments for HIV potentially slowing – or even preventing – the onset of AIDS.
The trial makes use of the body’s natural ability to recognise infected cells by enhancing the power of the T cell receptor (TCR) on killer T cells. When a virus infects cells, it hijacks the host cell machinery in order to replicate and spread infection. These infected cells then expose or “present” small parts of the virus proteins on their surface, offering a "molecular fingerprint" called an epitope for killer T-cells from the immune system to identify. This triggers an immune response, eliminating the virus and any cells involved in its production. However, HIV not only replicates itself quickly on infection but also has the ability to mutate rapidly, swiftly disguising its fingerprints to allow it to hide from killer T-cells.
Researchers at the Oxford University spin-out Adaptimmune have spent a decade working on ways to improve the natural ability of the TCR to recognise infected and cancerous cells; a process which has involved remaking the natural TCR protein and then modifying its ability to bind to the molecular fingerprints of the affected cells.
Last year, with colleagues at the University of Pennsylvania, they engineered and tested a killer T-cell receptor that can recognise all the different disguises HIV is known to have used to evade detection. The researchers transferred this receptor to the killer T-cells to create genetically engineered "bionic assassins" able to destroy HIV-infected cells in culture. Now, less than a year later, they are taking their unique technology into the clinic.
“The immune system uses T cell receptors to find and trigger the elimination of infected cells”, says Dr Bent Jakobsen, Chief Scientific Officer at Adaptimmune Ltd. “HIV, however, poses an intractable challenge because it has a phenomenal ability to escape detection through mutation whilst the immune system is not able to adapt its T cell receptors. Together with our colleagues at the University of Pennsylvania, we have previously shown that it is possible to engineer a T cell receptor that detects the known spectrum of HIV escape mutants for this particular fingerprint and triggers a more potent immune response when transferred into a patient’s cells. Today sees that important research result move into the clinic – for the first time allowing us to test the power of super potent immune cells against HIV in reality.”
The trial will be led by Carl June, MD of the Abramson Family Cancer Research Institute and the Department of Pathology and Laboratory Medicine alongside Pablo Tebas, MD, Director of the adult AIDS Clinical Trials Unit (ACTU), Department of Infectious Diseases Division at the University of Pennsylvania.