In oncology, targeted immunotherapies such as monoclonal antibodies specifically recognise and attack cancer cells, but despite generating strong initial anti-cancer responses with low toxicity, resistance frequently arises due to high mutation rates, allowing the cancer to return. Other therapeutic approaches, such as the checkpoint inhibitors anti-PD1/PDL1 and anti-CTLA-4, focus instead on taking the brakes off the immune system and creating a broader systemic anti-cancer response. While this approach has produced impressive results for individual patients, toxicity has been an issue and the majority of patients fail to generate a sufficiently strong immune response against the cancer.

The ImmTAC solution combines strong and specific targeting of cancer cells, with the potential to deliver -

• Broad and potent immune activation, able to recruit and redirect a patient’s own T cells regardless of the T cells natural antigen specificity
• Access to a pool of antigenic targets that is up to nine-fold greater than traditional antibody-based therapies

The unique and potent mechanism of action provided by ImmTAC molecules means that they can tackle diverse tumour types including the most frequent solid, or “cold”, low mutation rate tumours. ImmTAC molecules have potential application in both monotherapy and combination settings, with the latter providing an opportunity for synergistic effects and enhanced patient outcomes.

At Immunocore, we are applying our T cell receptor (TCR) platform outside of oncology to the discovery of new treatments for infectious diseases that pose a global health challenge. Immune mobilising monoclonal TCRs against virus (ImmTAV) and Immune mobilising monoclonal TCRs against bacteria (ImmTAB) molecules are small novel protein molecules that, like ImmTAC molecules, enable the immune system to recognise and kill diseased cells, in this case, virally or bacterially infected cells. 

Our initial target indications are:

• HIV: Despite improvements in treatment and prevention, there is no cure for the over 37 million people living with HIV, of whom just over half are aceessing treatment, or for the 5000 people who newly contract the virus every day.
• Chronic hepatitis B: There are over 250 million people worldwide chronically infected with HBV with the highest prevalence primarily in China, Southeast Asia and sub-Saharan-Africa.  Persistent HBV-infection of hepatocytes can lead to cirrhosis, hepatocellular carcinoma and end-stage liver failure, each of which contributes to the significant disease burden.
• Tuberculosis (TB): Chronic TB infection remains a major global health problem, with approximately 10 million new infections each year.

Our Infectious Diseases unit is deeply informed by our understanding of the mechanism of action of IMCgp100. We have also generated ex vivo pilot data showing that HIV-directed ImmTAV molecules redirect ART-treated patient T cells to kill HIV-infected cells, even with low antigen copy numbers per cell (Yang et al, 2016).

ImmTAV and ImmTAB molecules have the potential to reduce treatment timelines, improve patient outcomes and ultimately “functionally cure” infections for which no cure exists today. The development of ImmTAV/B technology is supported by The Bill & Melinda Gates Foundation, with an investment of up to $40 million. 

Yang H, Buisson S, Bossi G, Wallace Z, Hancock G, So Cet al. Elimination of latently HIV-infected cells from antiretroviral therapy-suppressed subjects by engineered immune-mobilizing T-cell receptors. Mol Ther (2016) 24:1913–25).

At Immunocore we are applying our T cell receptor (TCR) platform to generate unique and highly effective molecules against autoimmune diseases. ImmTAAI^TM (Immune mobilising TCRs against autoimmune disease) molecules constitute a targeted TCR fused to an effector function that is able to trigger immune suppression in a tissue of interest. 

Autoimmune diseases are very common, often chronic and debilitating, and constitute an area of high unmet clinical need. The American Autoimmune Related Diseases Association (AARDA) estimates that 50 million people suffer from autoimmune disease in North America alone and that the prevalence is rising, creating a substantial burden on society and healthcare systems.

The ultimate objective of our research is to provide a cure for autoimmune diseases by reconstituting the balance of the immune system. ImmTAAI molecules have the potential to selectively inhibit the over-active immune system in a particular organ or tissue, thereby directly targeting the disease cause without eliciting unwanted immune suppression in other parts of the body. We believe that this approach can address many shortcomings of current treatments and has the potential to deliver benefit to patients with no or limited treatment options.