The WT1 gene--its role in tumourigenesis and prospects for immunotherapeutic advances

The Wilms Tumour 1 (WT1) gene is a complex gene which was originally linked to suppression of cancer in kidneys. Studies of WT1-knockout mice confirmed the important role of WT1 in the pathogenesis of Wilms' tumour, a tumour which accounts for 95% of all childhood renal tumours. In such cases, the WT1 gene acts as a tumour-suppressor gene. Subsequent research has shown that the WT1 gene in many other cases acts as an oncogene, most prominently in leukaemia and lung cancer (even though these cancer forms can emerge as a result of many other aetiological factors). Since WT1 acts as an oncogene in many different organs, it is of great importance to evaluate how and when the WT1 gene and protein act. This information can then be used to develop immunotherapy to stabilize and treat different malignant diseases. Both phase I and phase II studies have been carried out on candidate vaccines with varying but overall promising results. The immune response does not always correlate with the clinical response, however, and the efficacy of the treatment is often limited. Further development is, therefore, needed to understand how vaccines can be improved, so that they, can hopefully fulfil a clinical role in the future.