Cytotoxic Agents with Immunosuppressive Activity

A whole variety of chemical and biological materials have immunosuppressive effects in animals. Although anti-inflammatory agents, especially the corticosteroids, are inhibitors of the immune response, most are general cytotoxic agents. The cytotoxic agents were first developed as antitumour agents. It is now well known that they are not particularly selective for cancer cells, but are selectively toxic for cells that are in cycle. Some are even more specific, acting only on cells in a particular phase of the cell cycle. When selective antitumour effects are obtained, this is not through a different mechanism of action, but is a result of other properties of the agent that ensure that a greater reaction takes place in the cancer cell than in sensitive cells of the host. This may be achieved by selective concentration or by selective activation of the agent in the cancer cell. Alternatively the compound may be more readily detoxified by normal cells or these may have a greater ability to repair any damage caused. As a result of their general cytotoxicity these antitumour agents have a number of side effects, most of which are undesirable, but which may sometimes be exploited, such as in their use as immunosuppressive agents. When these agents are used for their immunosuppressive properties their selectivity is once more determined by the properties of the whole molecule, which regulate the amount of agent reacting with the target sites of the immunocyte compared with the amount that reacts with sensitive host cells.