DNA vaccines against cancer: from genes to therapy.

After an erratic history, there is at last a clear opportunity for mobilizing an immune attack against cancer cells. The new strategies are dependent on the techniques of molecular biology, which are able both to identify potential target tumor antigens at the gene level, and to help to unravel the complexities of immune mechanisms required. Vaccine delivery systems can also be genetic, with DNA vaccines able to act as viral mimics and enter several antigen processing pathways. Rational vaccine designs can be rapidly tested in models and selected for pilot clinical trials. One difficulty faced by tumor antigens is that they may be weak, and therefore fail to engage the immune system. Attaching genes encoding alert signals appears to solve this problem. We have focused initially on idiotypic determinants of B-cell tumors, where the encoding variable region genes can induce protective anti-idiotypic immunity if delivered as a fusion protein with a fragment of Tetanus toxin. This model may have relevance for alternative tumor antigens. A clinical trial of patients with lymphoma is in progress, and wider application may be limited only by the ability to bring patients into clinical remission prior to vaccination.