Cancer antigens

Modern cancer immunotherapy began with the discovery that immune system cells, called T lymphocytes or T-cells, can recognize antigens on cancer cells, just as they can recognize them on cells infected by viruses or bacteria. In animal studies, researchers found that a type of T-cell called cytotoxic T-cells was responsible for the healing or regression of established lumps of cancer cells (tumors). The cytotoxic T-cells were able to destroy the individual abnormal cells marked out by the antigens.

Formation of cancer cells is directed, like formation of the normal cells in our body, by our genes. The genes in our cells normally control the way those cells grow, mature and divide. Genes contain coded instructions in the form of DNA. If certain genes become damaged or changed they can affect the way cells grow and develop, which can eventually lead to cancer development.

A possible consequence of damage or changes to genes is the production of abnormal proteins, which are detected and presented as antigens on the surface of the abnormal cells and are called cancer antigens. Cancer antigens vary in how specific to cancer cells they are, so some have greater potential for use in cancer immunotherapy than others.

Cancer-specific antigens

• Some antigens are cancer-specific and shared: this means that the antigen can be found in different forms of cancer, such as skin cancer, lung cancer and bladder cancer. The antigen is cancer-specific in the sense that it is not expressed by normal cells. Shared cancer-specific antigens are valuable candidates for cancer immunotherapy. An effective immune response against these antigens will be restricted to the cancer tissue only and not involve other, normal body tissue.
• Another type of antigen is not cancer-specific, meaning that the antigen can also be found in normal cells. Stimulation of an immune response against these antigens may also lead to damage or elimination of normal cells, and this could result in side effects.

Ideally, a cancer antigen should be cancer specific: it is only present in cancer tissue, not in normal tissue. An immune response would then only eliminate cancer cells without affecting other, normal and healthy tissue.

GSK has focused first on cancer-specific shared antigens for the development of its new ASCI (Antigen–Specific Cancer Immunotherapeutics) approach to cancer immunotherapy. The first of these to be tested in a large clinical study with cancer patients is called MAGE-A3. This antigen is found in a number of different types of cancer, including non-small cell lung cancer and melanoma, the targets of the first two major studies.