'Magic bullet' cancer therapy
The first-ever clinical trials are under way to test an innovative leukaemia treatment in which tumour-seekers carry radionuclide 'guns' to their cancer-cell targets. Background Alpha-immunotherapy is a new form of radiotherapy nicknamed `magic bullet' treatment. Each `bullet' is an alpha particle emitted by a radioactive isotope. Alpha radiation is extremely lethal but very short-ranged, so the alpha emitter is carried to its target by a protein, usually a monoclonal antibody, that binds specifically to certain molecules on the tumour-cell surface. Within ten minutes of administration, the cell-killing radioisotopes reach the targeted cancerous cells and stick to them throughout the half-life of the isotope (about 45 minutes) which decays into a non-radioactive substance. As few as one to two atoms of appropriately targeted `bullets' can kill a cancer cell, although they do little damage to the surrounding healthy tissues as their alpha radiation can travel no further than a few cell diameters. The strategy seems particularly suitable for treating blood-borne cancers, and is being tested for the first time on humans as a treatment for acute myelogenous leukaemia. Working partnerships These phase-1 clinical trials resulted from collaboration between the Institute of Transuranium Elements (ITU) of the European Commission's Joint Research Centre and the Memorial Sloan Kettering Cancer Center (MSKCC) in New York. As a key contributor to this research, ITU is involved in several other EC-supported projects focusing on treatment of multiple myeloma (INSERM, France), non-Hodgkin's lymphoma (University of Heidelberg, Germany), colon cancer (University of Gottingen, Germany), stomach cancer (Universitatskliniken Munchen, Germany), and low-grade glioma (Kantonsspital Basel, Switzerland). Description, impact and results In collaboration with the MSKCC, ITU first proposed a suitable alpha-emitter (Bismuth-213), then developed a safe, transportable kit containing a source of Bismuth-213, along with procedures for extracting the isotope in hospital. In preclinical tests, mice were cured of human cancer. In the ongoing phase-1 clinical trials, 17 patients have received the treatment - no complete remissions have occurred, but results are encouraging as the anti-leukaemia effect is significant and there have been no acute side effects. In addition to the direct treatment of patients, a second approach is envisaged in the context of bone marrow transplants and blood stem cell rescue: stem cells taken from patients about to receive high-dose chemotherapy or total body irradiation would be purged of any cancer cells by a Bismuth-213-coupled antibody, prior to their reinjection into the patient. ITU has already patented such a purging procedure. It is also interested in clinical applications of Actinium-225, the `mother nuclide' from which Bismuth-213 is formed, which is longer-living and possibly more suitable for treating larger or less-accessible tumours. Alpha-immunotherapy is a promising new strategy for selectively killing cancer cells and, with its wide range of potential applications, the magic bullets could benefit cancer patients world-wide.