Viruses capable of persistent or recurrent infections have evolved strategies to evade or subvert the host’s immune system. These strategies vary from relatively simple ones such as rapid antigen mutations to more complex, active modulation of the host’s immune system. However, whichever strategy the virus employs, the outcome is the same – the host’s immune system cannot bring the viral infection under control.

Immunocore’s viral antigen-specific ImmTACs are designed to target infected cells and mark them for immediate destruction by the killer T cells of the immune system, circumventing the immune avoidance strategies employed by the virus.

HIV

HIV employs a host of mechanisms to avoid detection by the immune system, a key one being the ability to disguise itself through mutating the antigens presented to the immune system by class I Human Leukocyte Antigen (HLA) proteins. These escape mutations provide the virus a window of opportunity to replicate and infect new cells before the T cells of the immune system can adapt to the new disguise.

Immunocore has developed a picomolar affinity ImmTAC reagent specific for a well validated HIV antigen called GAG. Importantly, this novel reagent recognises all of the known escape mutations employed by the virus and is designed to allow the immune system to control the virus, even if it mutates.

HCV

Hepatitis C often leads to lifelong, chronic infection resulting in cirrhosis of the liver and an elevated risk of developing liver cancer. Current standard of care, an 11-month course of interferon plus ribavirin, cures around 50% of infected patients. The next generation of HCV treatment will revolve around the use of proteosome inhibitors and is expected to increase cure rates to around 80% after 6 months of treatment. There is no effective treatment for the remaining 20%.

Immunocore is developing ImmTAC reagents that specifically target HCV infected cells and mark them for destruction. The potency of the ImmTAC therapeutic approach offers the potential to treat those patients not served by current or next generation standard of care. It could also significantly reduce overall treatment times from the current 6-11 months, thereby improving patient compliance.