A revolutionary cancer-targeting technology developed by researchers at Immunocore Limited has been described for the first time in the prestigious medical journal, Nature Medicine.
The new reagents known as ImmTACs (Immune Mobilizing mTCR against Cancer) mobilize T cells to kill cancer cells and overcome immune tolerance to cancer.
The most advanced of Immunocore’s ImmTACs, a drug called IMCgp100, is already in clinical trials in the UK and US for the treatment of melanoma.
A second oncology ImmTAC, IMCmage1, is set to enter the clinic in both countries later this year and is applicable to the treatment of a large number of poorly served cancer indications.
Antibody-based drugs have become a mainstay of cancer treatment, but their use is limited to the small fraction of cancer targets that present as whole proteins on the cell surface. Most cancer targets are hidden inside cancerous cells where antibodies cannot reach them.
By contrast, T cells employ T Cell Receptors (TCRs) which target the peptide antigens found on the cell surface as a marker of cancer and viral infection inside the cell.
TCRs can potentially target any of the markers that are hallmarks of cancer and enables the development of drugs against cancers for which no antibody targets are known.
Unfortunately, the TCRs found naturally on the surface of killer T cells are primarily designed to recognize virally infected cells, and are often not sensitive enough to recognize cancer, which is then ignored by the immune system.
The scientists at Immunocore have managed to overcome this cancer recognition problem by boosting the ability of cancer-specific TCRs to bind to their targets with several million fold higher affinity than natural TCRs.
The company has subsequently equipped these engineered TCRs with the ability to activate all the T cells of the body to kill cancer, even those that would normally not recognize cancer, thereby bringing the entire weight of the immune system to bear against the disease.
Immunocore calls this new class of therapeutics ImmTACs (Immune Mobilizing mTCR Against Cancer). Dr Bent Jakobsen, Immunocore’s chief scientific officer, said: “The main hindrance to better cancer treatments is finding ways of targeting malignant cells without harming the body’s normal cells too much. This is where TCRs are uniquely compelling: for TCRs, there are potentially more targets available than for all other types of cancer treatments combined.
“However, for decades it has been thought that there was too little of each target on each cancer cell for it to be possible to make a reagent with which to find them. It’s a great pleasure, after fifteen years of research by a dedicated team of scientists, to be able to say that we have finally solved this problem.”
James Noble, Immunocore’s CEO, said: “The power of this new technology lies in its ability to be used for a host of cancers that are currently very difficult to treat. We look forward to building on the emerging clinical data and generating a robust pipeline of products over the coming years.”