Safety Issues Related to Retroviral-Mediated Gene Transfer in Humans

The first three approved human clinical trials utilizing retroviral-mediated gene transfer are now underway. While this technology holds great promise for the study and treatment of human disease, it also poses a number of safety concerns. In evaluating clinical protocols, potential complications and the likelihood of their occurrence are estimated by review committees so that a risk/benefit assessment can be made. Current knowledge, reviewed in this article, suggests that no acute complications secondary to retroviral-mediated gene transfer are likely, but the possibility of long-term or unforeseen sequelae in patients suggests the need for post-treatment monitoring. A critical element in the evaluation of the present human gene transfer/therapy clinical protocols is an assessment of the risk factors associated with retroviral-mediated gene transfer. This review is an update of the document submitted to the RAC and the FDA during the approval processes for the N2/TIL gene transfer and the ADA and TNF/TIL gene therapy clinical protocols.