New horizons: gene therapy for cancer

Abstract

p53 gene mutations appear in numerous human cancers and are associated with anumber of cellular mechanism changes including a lack of apoptosis. Repeated intratumoral injection of the adenoviral p53 vector (Ad5CMV-p53) in patients with non-small cell lung cancer and head and neck cancer is feasible and well tolerated. Treatment results in expression of the p53 transgene and evidence of increased apoptosis. Dose-related antitumor activity has been seen in phase I trials in both lung and head and neck cancer. Transgene expression appears to occur even in patients who mount an immune response to the adenoviral vector. The evidence to date indicates that gene transfer can occur without contamination of health care workers by the vector. There is preliminary clinical evidence suggesting that the in vivo synergy seen between Ad5CMV-p53 and cisplatin may also occur in patients. Phase II trials are justified and have been started.