Cancer Immunotherapy

Our immune system protects us by distinguishing self from foreign substance and destroying foreign pathogens by means of antibodies and immune cells. Cancer cells are derived from normal cells and carry antigens on its surface, which may also be found on normal cells. The immune system can recognize cancer cells as foreign if cancer cells express certain antigens like protein molecules which are not seen in the normal cells. An antigen is any substance, which is capable of causing an immune response, such as specific antibody formation and specific T-lymphocyte activation. Antibodies are proteins of the immunoglobulin class that are produced by plasma cells on exposure to an antigen. Antibodies bind specifically to the antigen and thus contribute to its elimination by other components of the immune system.

Antigens unique to cancer cells can be detected using either serum from the host or from immunized animals. A major approach is based on monoclonal antibodies, i.e., antibodies produced by a single clone of B cells. Monoclonal antibodies consist of a homogeneous population of identical antibody molecules, all specific for a particular antigenic determinant.

There are three types of cancer-specific antigen:

When the cancer cells are recognized by the body's immune system, destruction of them may occur by either humoral or cellular mechanisms. Humoral mechanisms include lysis by antibody and complement, and antibody-mediated loss of cancer cell adhesion. Cellular mechanisms include destruction by cytotoxic T-cells, antibody-dependent, cell-mediated cytotoxicity, destruction by activated macrophages, and destruction by natural killer (NK) cells.

Researchers have demonstrated that vaccinating patients with their own cancer cells can cause the rejection of the cancer. It is intriguing why cancer cells can express foreign antigens. One possibility is that mutations in cancer cell genomes lead to abnormal genes and hence abnormal or foreign proteins. Alternatively, the transformation of normal into cancer cells can be caused by viral oncogenes, which code foreign proteins.

If cancer cells can be recognized as foreign entities by the immune system, why are they not removed right away? Here are some explanations. First, not all cancer cells can express cancer-specific antigens. Secondly, some cancer cells expressing certain foreign antigens are not sufficiently immunogenic and hence immunological response elicited is not strong enough to kill them. Thirdly, cancer cells may escape attack by immune cells through the mechanism of immune tolerance. It is probably true that cancer cells surviving immune attack are little immunogenic. How to boost the immunogenicity of cancer cells lies at the heart of cancer immunotherapy.

Cancer immunotherapy includes vaccination and adjuvant therapy against specific epitopes present on cancer antigens, cytokine therapy with certain cytokines such as alpha interferon, anti-idiotype monoclonal antibody therapy targeting the idiotype of the antigen, and immunotoxin therapy involving attachment of a toxin to a monoclonal antibody directed specifically to the cancer.