Adenovirus p53 gene therapy.

To date, dysfunctional tumour suppressor genes are the most common genetic lesions identified in human cancers. Functional copies of tumour suppressor genes can be introduced into cancer cells by gene transfer using adenoviral vectors. This approach has been extensively studied in the clinic with intratumoural injection of a replication-defective adenovirus that expresses p53 (Ad-p53). Overexpression of p53 in cancer cells induces growth arrest and apoptosis. Ad-p53 injections have an excellent safety profile, and have mediated tumour regression and growth arrest as monotherapy, or have overcome resistance or increased the effectiveness of radiation therapy and chemotherapy. Expression of the p53 transgene has occurred at high levels and is associated with the activation of other genes in the p53 pathway. These studies indicate proof-of-principle for tumour suppressor gene therapy and represent a new paradigm in targeted therapy.