As next-generation cancer treatments go, a new one looks extremely promising in pre-clinical laboratory testing. A small private biotechnology company in the UK, Immunocore, has invented a hybrid protein called an ImmTAC (Immune Mobilizing mTCR Against Cancer) that will attach itself to targets on cancer cells and cause immune cells to directly kill the cancer cell on contact. Videos of T cells essentially throwing around cancer cells like rag dolls and killing them can be found here.

GlaxoSmithKline (GSK), the largest pharmaceutical company in the UK, will give the company up to $212 million for milestones achieved during laboratory testing before clinical trials on people take place. Immunocore will also receive an additional $200 million pounds for each product brought to market and greater than 10 percent in royalties from sales. The company will be responsible for all pre-clinical testing as well as initial clinical trials in patients, while GSK will deal with the late-stage clinical trials, approvals, and commercialization of the drugs.

The key to this treatment is that it can cause an immune reaction to proteins normally only found inside, rather than on the surface, of cancer cells. Typical next-generation anti-cancer treatments, such as Herceptin for breast cancer, are monoclonal antibodies (mAB) that are only one type of antibody that stick to a specific receptor on the surface of cancer cells. In the case of Herceptin, the antibody only binds to the Her2 receptor, and immune cells then attack the cancer cells that have the receptor on their surface. The limitation of this technology is that it can only target surface molecules or receptors on cancer cells and not the vast majority of proteins inside of the cancer cell.

This new technology, however, exploits a biological response to viral infections and cells becoming cancerous. These cells typically express a receptor called MHC Class I on their surface. This is a receptor that signals to the immune system that there is something wrong with the cell and that it should be investigated. MHC Class I also presents a piece of some broken down proteins from inside of the cell, and in the case of a virally infected cell, it presents part of a virus. Cancer cells may present pieces of mutated proteins that are found only within the cell and may be indicative of a specific type of cancer.

Monoclonal antibodies (mAB) tot he left can only see surface proteins on cells. Monoclonal T cell Receptors (mTCR) can recognize portions of proteins from inside of the infected or cancerous cell.

Immunocore's ImmTACs are genetically engineered proteins that have two specific ends. One end would be the same receptor on T cells of the immune system, called a T Cell Receptor (TCR). This monoclonal (only one kind) TCR would be specific for some internal protein segment being presented on the MHC I of a cancerous cell or virally infected cell. The other end of the specialized protein would be part of an antibody specific for CD3. Antibodies that bind to the CD3 receptor on T cells activate the T cells wildly and with extreme strength, regardless of the T cell specificity. (Each T cell is specific for something different. For example, one may be specific for a component of the flu virus and another specific for a component of a pathogenic bacteria like Salmonella.)

So essentially, this genetically engineered protein bypasses the individual specificity of T cells and allows them to become activated in response to specific viral or cancerous proteins. With a previous investment from Genentech, a subsidiary of Roche, valued at $10-20 million for each program and more than $300 million for commercial and developmental milestones, it seems that the technology is poised to be a game changer.

A review of the ImmTAC technology can be found here.