Gene therapy of solid tumors and hematopoietic neoplasms.

Abstract

The ultimate goal in cancer treatment is to identify and correct at the molecular level the derangements that cause the various human malignancies. Important scientific discoveries about the mechanisms through which cancer develops are increasing the likelihood that the introduction of foreign genetic material into mammalian cells may be used as a primary method of therapy. Genetic modification of malignant and nonmalignant cells can be performed on the patient (in vivo) or on cells removed from the body (ex vivo) with subsequent reinfusion into the patient. Delivery systems in gene therapy strategies have included transduction mediated by retrovirus, adenovirus, liposomes, and direct injection of DNA (table 1). Genetic manipulations aimed at correcting disease processes at the molecular level have already been introduced into clinical trials. There are now over 100 cancer treatment trials involving gene transfer or antisense treatment, according to the records of regulatory committees worldwide. These trials involve both gene marking trials and trials based on the use of genetic modification designed for activation of the immune system, chemoprotection of hematopoietic cells, or chemosensitization of tumor cells. The major obstacles to gene therapy in cancer have been selectivity, transduction frequencies, stability of transduction, and effectiveness due to the complexity of genetic alterations found in human tumors.