Alexander Fleming

Back In 1895 Hericourt and Richet described the first trials in which cancer cells were injected into animals to raise an antiserum for treating the

patient. None of them were cured, but they showed significant improvements in their symptoms. During the early 1900\'s many workers repeated these trials, but found nothing, leading to the conclusion in 1929 that nothing will work. It was discovered that an antiserum contains a mixture of many different antibodies, each one directed against a different antigen on the cancer cells. Many of these antigens are also present on normal tissue cells and so the antibodies against them could be harmful. In 1975 Kohler and Milstein found what first envisaged 80 years earlier. Since then a prodigious number of different monoclonal

antibodies have been made and they have been exploited in almost every

branch of biomedical research. Several have been found which recognise human

cancers and some of these have been tested in clinical trials. The first studies relied on the intrinsic ability of the antibody molecules to recruit the body's own defence mechanisms to kill tumour cells. When these natural mechanisms were found to be insufficient, various artificial warheads were proposed including conventional chemical drugs, and plant toxins. Now there are so many potential combinations of guidance system and warhead that we can test only a small fraction. However, we have learned some important lessons. Therapy with antibodies is limited by the ability of the patient's immune system to detect the new substance and neutralise it. This means there is only a short time when antibody therapy can be used before it becomes ineffective. More fundamentally, the sheer numbers of tumor cells in patients with terminal disease overwhelm the therapy. Some cells express too little antigen to be targeted and cells in a large mass may escape attention altogether. Antibody therapy is most likely to be useful in the context of minimal, but disseminated disease; in fact just the situation that often occurs after conventional chemo-radiotherapy. This concept is not new; it was already foreseen by Hericourt and Richet in 1895. However, it is hard to tell whether the treatment of minimal disease is beneficial since it is

difficult to measure an immediate effect. Instead we must wait to see