(Oxford, UK, 6th May 2012) 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 Mobilising mTCR against Cancer) mobilise 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 recognise virally infected cells, and are often not sensitive enough to recognise 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 recognise cancer, thereby bringing the entire weight of the immune system to bear against the disease.
Immunocore calls this new class of therapeutics ImmTACs (Immune Mobilising 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.”
PR Consultant, Immunocore Ltd, UK
T: +44 (0)1865 261491 M: 07771 377363 E: firstname.lastname@example.org
Images available on request
1. A video showing Monoclonal TCR-redirected tumour cell killing is available on request.
It can also be viewed online at: http://www.immunocore.com/technology/cancer-killing/
2. Stills images are available showing the serial killing of three melanoma cells (red) by a single non-cancer-specific T cell (green) in the presence of the drug, IMCgp100.
Liddy et al (2012) Monoclonal TCR-redirected tumour cell killing, Nature Medicine, published online on 6 May 2012 (visit: http://dx.doi.org/10.1038/nm.2764)
A copy of the paper is available on request.
Immunocore Limited is developing innovative biological therapeutics to treat a range of cancers, chronic viral infections and diabetes. Immunocore is a privately owned biotechnology company located at Milton Park, near Oxford. The company traces its roots back to Avidex Limited which was founded in 1999 as a spin-out from the University of Oxford to develop technology invented by the founder and chief scientist, Dr Bent Jakobsen. Avidex was acquired in 2006 by the German company MediGene AG. In 2008, MediGene spin out two independent companies based on the same core TCR enhancement technology platform; Immunocore to develop soluble protein therapeutics and Adaptimmune to develop cellular therapies. (www.immunocore.com).
IMCgp100 is a product derived from Immunocore’s ImmTAC™ technology platform.
ImmTACs couple the unique ability of affinity-enhanced T Cell Receptors (TCRs) to target cancer and virally infected cells based on intracellular antigens that cannot be treated using traditional antibody-based approaches, with a highly potent anti-CD3 mediated T cell redirection system.
Immunocore has developed processes that allow it to isolate human TCRs specific for a target of interest and to create soluble versions whose affinity has been enhanced several million fold. These engineered, disease -specific, TCRs are fused to an antibody fragment that binds a cell surface protein called CD3 which is found on the surface of the killer T cells of the immune system. ImmTACs target the diseased cells and redirect any T cell touching them to kill, even if that T cell would normally only recognise other diseases such as the common cold.
Unlike traditional immunotherapies such as cancer vaccines or immune-stimulating agents such as anti-CTLA4 antibodies, Immunocore’s ImmTACs have been specifically designed to overcome the antigen down-regulation that has limited the effectiveness of immunotherapies to date. Pre-clinical tests indicate that they can achieve potent T cell redirection against cancer cells that have lost almost all of their cell surface antigens through down-regulation.
IMCgp100 is an ImmTAC reagent specific for a peptide derived from the well validated target protein gp100, presented by HLA-A2; this target being present in approximately 50% of melanoma patients. IMCgp100 demonstrates potent activity against melanoma cells in vitro, including cancer stem cells.
About Metastatic melanoma
Melanoma is a form of skin cancer that accounts for less than 5% of cases, but causes the vast majority of skin cancer deaths. The American Cancer Society estimates that about 68,130 new melanomas will be diagnosed in the United States during 2010 (about 38,870 in men; 29,260 in women) and 8,700 deaths from this disease will occur. 10, 672 cases were diagnosed in the UK in 2007 and there were 2,067 deaths in 2008. Incidence rates for melanoma have increased in the last thirty years and, unlike other common cancers, melanoma has a wide age distribution. In recent years, the increases have been most pronounced in young white women and older white men (www.cancer.org; www.cancerresearchuk.org).
Patients who are diagnosed early are treatable with surgical resection, although in many the disease will recur within a few years. If melanoma continues to the late stages and becomes metastatic, the prognosis is poor, with average survival rates of only six to nine months. Chemotherapy is the most common treatment for patients with metastatic melanoma, but the response rate is very low. There is a high level of unmet need for more effective therapies.
IMCmage1 is an ImmTAC reagent specific for the well validated target proteins MAGE-A3 and MAGE-A6, presented by HLA-A1. The MAGE proteins targeted by IMCmage1 are members of the cancer/testis antigen family that are expressed in a wide variety of solid and haematologic cancers such as NSCLC, SCLC, hepatocellular carcinoma and colorectal cancers. The MAGE proteins represent some of the best validated, truly cancer specific targets known, but their clinical utility has been limited to date, as their intracellular location has prevented the development of targeted therapies such as antibodies.